4.6 Review

Tau-targeting therapies for Alzheimer disease: current status and future directions

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Review Cell Biology

Tau Aggregation Inhibiting Peptides as Potential Therapeutics for Alzheimer Disease

Isabelle Aillaud et al.

Summary: Alzheimer's disease is a common progressive neurodegenerative disorder with limited treatment options. The pathology of Tau protein is closely correlated to clinical symptoms, making it a promising therapeutic target.

CELLULAR AND MOLECULAR NEUROBIOLOGY (2023)

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Phosphorylated tau sites that are elevated in Alzheimer's disease fluid biomarkers are visualized in early neurofibrillary tangle maturity levels in the post mortem brain

Christina M. Moloney et al.

Summary: This study aims to characterize the recognition of phosphorylated tau sites in early neurofibrillary tangle maturity levels, which may explain why these fluid biomarkers can be observed before symptom onset.

ALZHEIMERS & DEMENTIA (2023)

Article Medicine, General & Internal

Lecanemab in Early Alzheimer's Disease

Christopher H. van Dyck et al.

Summary: Lecanemab, a humanized monoclonal antibody, reduced amyloid markers and showed improvement in cognition and function in early Alzheimer's disease patients. However, it also resulted in adverse events. Longer trials are needed to determine its efficacy and safety in early Alzheimer's disease.

NEW ENGLAND JOURNAL OF MEDICINE (2023)

Review Biochemistry & Molecular Biology

Scrutinizing the Therapeutic Potential of PROTACs in the Management of Alzheimer's Disease

Shiveena Bhatia et al.

Summary: This article explores the application of PROTAC technology in treating Alzheimer's disease, which can manage the disease by degrading abnormal protein debris, demonstrating advantages over traditional drugs.

NEUROCHEMICAL RESEARCH (2023)

Article Biochemistry & Molecular Biology

Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer's disease: a phase 1b, randomized, placebo-controlled trial

Catherine J. Mummery et al.

Summary: By inhibiting MAPT expression with a tau-targeting antisense oligonucleotide (MAPTRx), researchers were able to reduce tau levels in patients with mild Alzheimer's disease. A randomized, double-blind trial found that the CSF total-tau protein concentration decreased by more than 50% in patients treated with MAPTRx, with mild adverse effects reported.

NATURE MEDICINE (2023)

Article Multidisciplinary Sciences

Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models

Aamir S. Mukadam et al.

Summary: Passively transferred antibodies can target and protect against tau pathology in neurodegenerative diseases. The cytosolic Ab receptor and E3 ligase TRIM21 have been identified as potential mechanisms of antibody protection against tau aggregation.

SCIENCE (2023)

Article Multidisciplinary Sciences

Single-domain antibody-based noninvasive in vivo imaging of α-synuclein or tau pathology

Yixiang Jiang et al.

Summary: Intracellular deposition of alpha-synuclein and tau are hallmarks of synucleinopathies and tauopathies, respectively. Suitable imaging biomarkers for synucleinopathies are still unavailable, while several dye-based imaging probes for tau aggregates have been developed. Small antibody derivatives derived from llama phage display libraries allow noninvasive and specific in vivo imaging of alpha-synuclein and tau pathology in mice, showing great potential for in vivo diagnosis of these diseases.

SCIENCE ADVANCES (2023)

Article Clinical Neurology

Tilavonemab in early Alzheimer's disease: results from a phase 2, randomized, double-blind study

Hana Florian et al.

Summary: Tau accumulation in patients with Alzheimer's disease is closely related to cognitive decline. This study evaluated tilavonemab, an anti-tau monoclonal antibody, in treating patients with early Alzheimer's disease. The results showed that tilavonemab did not demonstrate efficacy in treating early Alzheimer's disease.
Article Medicine, General & Internal

Donanemab in Early Symptomatic Alzheimer Disease The TRAILBLAZER-ALZ 2 Randomized Clinical Trial

John R. Sims et al.

Summary: This study evaluated the efficacy and adverse events of donanemab, an antibody treatment for Alzheimer's disease. The findings showed that donanemab significantly slowed disease progression in patients with early symptomatic Alzheimer's disease.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2023)

Article Biochemistry & Molecular Biology

CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer's disease

Kanta Horie et al.

Summary: Aggregated insoluble tau is a defining feature of Alzheimer's disease, and there is a need for specific fluid biomarkers to track these tau aggregates. However, current fluid biomarkers are not specific enough. Researchers have identified a new cerebrospinal fluid biomarker, MTBR-tau243, which is specific for insoluble tau aggregates and shows strong associations with tau-positron emission tomography and cognitive measures.

NATURE MEDICINE (2023)

Article Clinical Neurology

Randomized Phase II Study of the Safety and Efficacy of Semorinemab in Participants With Mild-to-Moderate Alzheimer Disease: Lauriet

Cecilia Monteiro et al.

Summary: The study investigated the effect of the anti-tau monoclonal antibody, semorinemab, in patients with mild-to-moderate AD. While it showed a positive impact on cognition, it did not improve functional or global outcomes.

NEUROLOGY (2023)

Article Medicine, General & Internal

Donanemab in Early Symptomatic Alzheimer Disease The TRAILBLAZER-ALZ 2 Randomized Clinical Trial

John R. Sims et al.

Summary: This study assessed the efficacy and adverse events of donanemab, an antibody designed to clear brain amyloid plaque. The results showed that donanemab significantly slowed the clinical progression in individuals with early symptomatic Alzheimer disease and low/medium tau pathology, as well as in the combined population with low/medium and high tau pathology.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2023)

Article Clinical Neurology

Tubulin tyrosination regulates synaptic function and is disrupted in Alzheimer's disease

Leticia Peris et al.

Summary: Microtubules are important for neuronal processes, synaptic function, and plasticity. The balance between tubulin tyrosination and detyrosination is crucial for maintaining microtubule dynamics and neuronal homeostasis. This study reveals that decreased tubulin tyrosine ligase expression is associated with Alzheimer's disease and leads to memory impairment and reduced synaptic integrity. Restoring microtubule entry into dendritic spines through tubulin retyrosination can protect against amyloid-beta peptide-induced synaptic damage.
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Inhibition of caspase-1 ameliorates tauopathy and rescues cognitive impairment in SAMP8 mice

Meng-Shan Tan et al.

Summary: This study found that caspase-1 was activated during the aging process in SAMP8 mice, and provided evidence that the selective inhibitor VX-765 significantly improved early-stage AD pathology, possibly through IL-1 beta-induced hypoactivation of tau kinases.

METABOLIC BRAIN DISEASE (2022)

Article Biotechnology & Applied Microbiology

Inhibition of Tau seeding by targeting Tau nucleation core within neurons with a single domain antibody fragment

Clement Danis et al.

Summary: The study demonstrates the effectiveness of VHH Z70 in inhibiting Tau aggregation and reducing pathological Tau accumulation in brain neurons. By specifically targeting Tau within cells, VHH Z70 provides an immunological tool for targeting the intra-cellular compartment in tauopathies.

MOLECULAR THERAPY (2022)

Article Clinical Neurology

Pathogenic cis p-tau levels in CSF reflects severity of traumatic brain injury

Alireza Mohsenian Sisakht et al.

Summary: This study investigates the correlation between cerebrospinal fluid (CSF) levels of cis phosphorylated tau protein and the severity of traumatic brain injury (TBI). The results show that the levels of cis phosphorylated tau in the CSF are significantly higher in TBI patients compared to controls, and vary according to the severity of the head injury. Additionally, there is a clear negative correlation between CSF cis phosphorylated tau levels and GCS scores.

NEUROLOGICAL RESEARCH (2022)

Article Neurosciences

Membrane channel hypothesis of lysosomal permeabilization by beta-amyloid

Dmitry V. Zaretsky et al.

Summary: Alzheimer's disease, the most common cause of dementia, is caused by neuronal death initiated by amyloid-beta peptides. This study proposes the amyloid degradation toxicity hypothesis, which explains the cellular toxicity of amyloid through the formation of non-selective membrane channels in lysosomal membranes. The formation of these channels is promoted in an acidic environment, leading to cell death.

NEUROSCIENCE LETTERS (2022)

Review Cell Biology

Targeting tau only extracellularly is likely to be less efficacious than targeting it both intra- and extracellularly

Erin E. Congdon et al.

Summary: The aggregation of tau protein is believed to be the main cause of tauopathies, and current treatment methods mainly focus on preventing or clearing these aggregates. Immunotherapies, which aim to stimulate the production of endogenous tau antibodies or deliver exogenous ones, are the most common approach in clinical trials. However, the majority of pathological tau protein is found intracellularly, which is surprising considering the current focus on extracellular tau clearance.

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2022)

Review Immunology

Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment

Jiewen Wang et al.

Summary: Recombinant antibodies like nanobodies are proving to be a valuable alternative to conventional monoclonal antibodies in clinical applications, with unique features that expand biotherapeutic options and alter disease treatment paradigms.

FRONTIERS IN IMMUNOLOGY (2022)

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Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease 2019

Emma Nichols et al.

Summary: With projected trends in population ageing and growth, the number of people with dementia is expected to increase. Understanding the distribution and magnitude of anticipated growth is crucial for public health planning and resource prioritization, with a focus on potentially modifiable risk factors.

LANCET PUBLIC HEALTH (2022)

Review Cell Biology

Glial cells in Alzheimer?s disease: From neuropathological changes to therapeutic implications

Lee Wei Lim et al.

Summary: Alzheimer's disease is a neurodegenerative disorder with unclear pathogenesis. Recent research suggests that microglia and astrocytes may play a role in the development of AD and could be potential therapeutic targets.

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Highly Specific and Sensitive Target Binding by the Humanized pS396-Tau Antibody hC10.2 Across a Wide Spectrum of Alzheimer's Disease and Primary Tauopathy Postmortem Brains

Lone Helboe et al.

Summary: This study investigated the heterogeneity of tau pathology across different tauopathies and evaluated the binding properties of the humanized pS396-tau antibody hC10.2 and other anti-tau antibodies. The findings showed that hC10.2 is a promising therapeutic tau antibody for the treatment of AD and primary tauopathies.

JOURNAL OF ALZHEIMERS DISEASE (2022)

Review Neurosciences

Tauopathies: new perspectives and challenges

Yi Zhang et al.

Summary: In this article, emerging knowledge on tauopathies from clinical, pathological, genetic, and experimental studies is synthesized to accelerate the development of therapeutics for these diseases. The focus is on depicting pathological characteristics, identifying biomarkers, elucidating the underlying pathogenesis for early diagnosis, and the development of disease-modifying therapies.

MOLECULAR NEURODEGENERATION (2022)

Article Neurosciences

Faulty autolysosome acidification in Alzheimer's disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques

Ju-Hyun Lee et al.

Summary: This study reveals unique autophagy dysregulation within neurons in Alzheimer's disease mouse models, particularly deficient autolysosome acidification, leading to the accumulation of autophagic vacuoles and the formation of flower-like structures called "PANTHOS," which may contribute to the development of senile plaques in Alzheimer's disease.

NATURE NEUROSCIENCE (2022)

Review Clinical Neurology

AAV Vector-Mediated Antibody Delivery (A-MAD) in the Central Nervous System

Marika Marino et al.

Summary: Monoclonal antibodies and their derivatives are powerful therapeutics due to their targeting specificity, but their use in Central Nervous System diseases has been slow due to limited Blood Brain Barrier permeability. However, as CNS diseases become more prevalent, there is a growing need to utilize the therapeutic potential of monoclonal antibodies. Adeno-associated virus-based vectors show promise in delivering antibodies to the CNS and could be used to target CNS proteinopathies.

FRONTIERS IN NEUROLOGY (2022)

Review Immunology

Tau immunotherapy in Alzheimer?s disease and progressive supranuclear palsy

Nastaran Karimi et al.

Summary: Tau, a protein associated with more than 25 neurological disorders, has been the target of research for finding novel therapeutic agents. This article reviews the latest animal and clinical studies on tau-based immunotherapies and drugs for Alzheimer's disease and progressive supranuclear palsy.

INTERNATIONAL IMMUNOPHARMACOLOGY (2022)

Article Biochemistry & Molecular Biology

Common and Specific Marks of Different Tau Strains Following Intra-Hippocampal Injection of AD, PiD, and GGT Inoculum in hTau Transgenic Mice

Isidro Ferrer et al.

Summary: Heterozygous hTau mice were used to study tau seeding and it was found that different tau strains produce different patterns of active neuronal seeding, which also depend on the host tau.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Biochemistry & Molecular Biology

CSF tau microtubule-binding region identifies pathological changes in primary tauopathies

Kanta Horie et al.

Summary: Currently, there are no fluid biomarkers or imaging tracers available for the diagnosis and treatment of other tauopathies. This study identifies specific tau species that increase in the brains of patients with CBD, PSP, FTLD-MAPT, and AD, but decrease in their cerebrospinal fluid. Measurements of these specific tau species in cerebrospinal fluid can differentiate between different diseases and aid in the diagnosis and clinical trial design of primary tauopathies.

NATURE MEDICINE (2022)

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A call for better understanding of target engagement in Tau antibody development

Anton Bespalov et al.

Summary: This article highlights the key factors for improving the translatability of Tau-based immunotherapy.

DRUG DISCOVERY TODAY (2022)

Review Neurosciences

The hippocampal sparing subtype of Alzheimer's disease assessed in neuropathology and in vivo tau positron emission tomography: a systematic review

Daniel Ferreira et al.

Summary: This study examines different subtypes of Alzheimer's disease (AD) using neuropathology and neuroimaging techniques, and finds that tau PET can identify hippocampal sparing AD cases with neurofibrillary tangles (NFT) completely sparing the hippocampus.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2022)

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Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer's disease

Marcos Otero-Garcia et al.

Summary: This study investigates the relationship between Tau protein aggregation in neurofibrillary tangles (NFTs) and Alzheimer's disease (AD). Through high-throughput isolation and transcriptome profiling, the researchers found that NFT-bearing neurons show an upregulation of genes related to synaptic transmission, particularly genes involved in synaptic vesicle cycling. They also observed that mitochondrial dysfunction and oxidative phosphorylation vary among different cell types. Interestingly, the susceptibility to apoptosis and death is similar between NFT-bearing and NFT-free neurons.

NEURON (2022)

Article Multidisciplinary Sciences

α-Synuclein fibril-specific nanobody reduces prion-like α-synuclein spreading in mice

Yemima R. Butler et al.

Summary: Butler et al. selected disulfide bond-free nanobodies to target alpha-synuclein fibrils. Nanobody PFFNB2 was shown to disaggregate alpha-synuclein fibrils in vitro and inhibit alpha-synuclein pathology development in neuron cultures and mouse models.

NATURE COMMUNICATIONS (2022)

Review Pharmacology & Pharmacy

The contribution of altered neuronal autophagy to neurodegeneration

Alessia Filippone et al.

Summary: Defects in cellular functions related to altered protein homeostasis and accumulation of pathological intracellular material play a critical role in the pathogenesis of neurodegenerative disorders. Autophagy is an essential mechanism for maintaining neuronal health and preventing cell toxicity and death. The autophagy pathways in neurons are altered in Alzheimer's disease, Parkinson's disease, and traumatic injuries to the central nervous system. Understanding the role of altered neuronal autophagy in brain health and developing novel therapeutics is of great importance.

PHARMACOLOGY & THERAPEUTICS (2022)

Article Medicine, General & Internal

Single domain antibodies targeting pathological tau protein: Influence of four IgG subclasses on efficacy and toxicity

Erin E. Congdon et al.

Summary: The study suggests that tau antibodies with effector function are safer and more effective in clearing pathological tau. Tau antibodies can provide valuable insights into tau pathogenesis, but some may worsen the condition.

EBIOMEDICINE (2022)

Article Cell Biology

Crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in Alzheimer's disease

Jose Martinez-Hernandez et al.

Summary: This study found an accumulation of tubulin acetylation in post-mortem brain tissues from Alzheimer's disease patients and human neurons with the Alzheimer's familial APP-V717I mutation. Impaired tubulin re-tyrosination may contribute to this acetylation accumulation.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

Article Biochemistry & Molecular Biology

Site-Specific Phospho-Tau Aggregation-Based Biomarker Discovery for AD Diagnosis and Differentiation

Ling Wu et al.

Summary: Tau aggregates, a characteristic feature of tauopathies, can be differentiated and used as potential biomarkers using site-specific phospho-tau antibodies. We identified several novel phosphorylation sites and showed that p-tau198 is a promising AD biomarker that can also discriminate related tauopathies. Our work provides a new avenue for diagnosis and differentiation tools for AD and related tauopathies.

ACS CHEMICAL NEUROSCIENCE (2022)

Article Clinical Neurology

Neuroinflammation co‐localizes highly with tau in amnestic mild cognitive impairment

Johanna Appleton et al.

Alzheimers & Dementia (2022)

Article Clinical Neurology

2022 Alzheimer's disease facts and figures

Joseph Gaugler et al.

Summary: This article discusses the impact of Alzheimer's disease on public health, including its incidence, prevalence, mortality and morbidity rates, healthcare costs and caregivers' burden. It also addresses the perspectives of consumers and primary care physicians on mild cognitive impairment (MCI) and the need for improved awareness, diagnosis, and treatment. The article emphasizes the increasing number of individuals living with Alzheimer's and the challenges faced by caregivers and healthcare providers, particularly during the COVID-19 pandemic.

ALZHEIMERS & DEMENTIA (2022)

Review Cell Biology

Past, present and future of therapeutic strategies against amyloid-β peptides in Alzheimer's disease: a systematic review

Danko Jeremic et al.

Summary: Alzheimer's disease is the most common neurodegenerative disease in aging population with lack of effective treatments. Accumulation of Aβ peptides is considered one of the fundamental neuropathological pillars of the disease, thus many therapies target Aβ.

AGEING RESEARCH REVIEWS (2021)

Article Clinical Neurology

Exosomes induce endolysosomal permeabilization as a gateway by which exosomal tau seeds escape into the cytosol

Juan Carlos Polanco et al.

Summary: The study revealed that tau seeds in tauopathies spread trans-synaptically via exosomes, escaping endosomes through lysosomal degradation to induce tau aggregation in the cytosol. The enzymatic activities of lysosomes permeabilize exosomal and endosomal membranes, facilitating access of exosomal tau seeds to cytosolic tau for aggregation. This highlights the crucial role of endosomal membrane integrity in cellular invasion by misfolded proteins resistant to lysosomal degradation.

ACTA NEUROPATHOLOGICA (2021)

Article Clinical Neurology

CSF tau microtubule binding region identifies tau tangle and clinical stages of Alzheimer's disease

Kanta Horie et al.

Summary: The study analyzed MTBR-Tau species in Alzheimer's disease and control CSF using sequential immunoprecipitation and chemical extraction methods followed by mass spectrometry. The species containing the region beginning at residue 243 were found to be highly correlated with tau PET and cognitive measures. This suggests that CSF level of tau species containing the upstream region of MTBR may serve as biomarkers to stage Alzheimer's disease and track the development of tau-directed therapeutics.
Article Neurosciences

A Single-Chain Variable Fragment Antibody Inhibits Aggregation of Phosphorylated Tau and Ameliorates Tau Toxicity in vitro and in vivo

Sen Li et al.

Summary: A new potential therapeutic agent against AD, the scFv T1 antibody, was screened in this study. It showed strong ability to inhibit tau aggregation in dilute solutions and under conditions of macromolecular crowding, and could depolymerize preformed tau aggregates in vitro, indicating its potential for treating neurodegenerative diseases.

JOURNAL OF ALZHEIMERS DISEASE (2021)

Article Chemistry, Multidisciplinary

Development of Antibody-Based PROTACs for the Degradation of the Cell-Surface Immune Checkpoint Protein PD-L1

Adam D. Cotton et al.

Summary: AbTACs are fully recombinant bispecific antibodies that recruit membrane-bound E3 ligases for the degradation of cell-surface proteins. This new archetype represents a method within the PROTAC field to target cell-surface proteins with fully recombinant biological molecules.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

Review Clinical Neurology

Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?

Fangda Leng et al.

Summary: Microglial activation and neuroinflammation play important roles in Alzheimer's disease, affecting disease progression and pathologies. Current research focuses on the interplay between neuroinflammation and amyloid and tau pathologies, with a specific interest in modulating microglia as a therapeutic strategy for AD.

NATURE REVIEWS NEUROLOGY (2021)

Article Neurosciences

Increased neuronal activity in motor cortex reveals prominent calcium dyshomeostasis in tauopathy mice

Qian Wu et al.

Summary: Perturbed neuronal Ca2+ homeostasis is closely related to Alzheimer's disease, with abnormal activity observed in tauopathy mice compared to wild-type mice. The study also found that tau monoclonal antibody injections partially rescued Ca2+ activity abnormalities and decreased soluble pathological tau protein in the brain of tauopathy mice. These results suggest a causal link between neuronal Ca2+ dyshomeostasis and pathological tau protein, highlighting the potential of acute tau antibody treatment in correcting neuronal Ca2+ dysregulation.

NEUROBIOLOGY OF DISEASE (2021)

Review Clinical Neurology

Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation

Carolina Alquezar et al.

Summary: Post-translational modifications play a crucial role in regulating tau protein function, including phosphorylation and acetylation. While these modifications may regulate protein function under normal conditions, they can be hijacked in disease states. Limited understanding exists on how these modifications impact tau protein, but studies indicate their critical role in localization, interactions, and other aspects.

FRONTIERS IN NEUROLOGY (2021)

Review Biology

Tau Oligomers Neurotoxicity

Grazyna Niewiadomska et al.

Summary: Tau oligomers (TauOs) formed during the early stages of tau aggregation play a key role in triggering neuronal loss and behavioral impairments in tauopathies like Alzheimer's disease.

LIFE-BASEL (2021)

Article Chemistry, Multidisciplinary

A Tauopathy-Homing and Autophagy-Activating Nanoassembly for Specific Clearance of Pathogenic Tau in Alzheimer's Disease

Heng Sun et al.

Summary: The study introduces a promising nanotechnology-based strategy for tauopathy-homing and autophagy-mediated specific removal of pathogenic tau in Alzheimer's disease (AD), showing selective accumulation in cells undergoing tauopathy and promoting clearance of pathogenic tau accumulation, consequently improving neuron viability and cognitive functions in AD rats.

ACS NANO (2021)

Letter Clinical Neurology

Neuropathology of progressive supranuclear palsy after treatment with tilavonemab

Shunsuke Koga et al.

LANCET NEUROLOGY (2021)

Article Geriatrics & Gerontology

Distinct phosphorylation profiles of tau in brains of patients with different tauopathies

Nastaran Samimi et al.

Summary: Different tauopathies exhibit distinct phosphorylation patterns of tau protein, with similar patterns within the same tauopathy. Some tauopathies may consist of different related diseases. AD, Pick's disease, and AGD patients display different site-specific phosphorylation in the brain, but a similar pathological mechanism may occur in AD and AGD patients.

NEUROBIOLOGY OF AGING (2021)

Article Clinical Neurology

Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial

Guenter U. Hoeglinger et al.

Summary: This study evaluated the safety and efficacy of tilavonemab in treating progressive supranuclear palsy, a neurodegenerative disorder. However, no beneficial treatment effects were observed and the study was terminated due to futility criteria being met. The findings suggest a similar safety profile across all treatment groups, with potential implications for future investigations using tau antibodies for progressive supranuclear palsy.

LANCET NEUROLOGY (2021)

Article Medicine, General & Internal

Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy: protocol for a phase 2, randomised, double-blind, placebo-controlled trial

Lucy Vivash et al.

Summary: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with no currently available disease-modifying therapies. This study aims to evaluate the efficacy and safety of sodium selenate as a potential disease-modifying therapy for PSP through a multi-site, phase 2b, double-blind, placebo-controlled trial. The primary outcome will be the change in MRI volume composite over the treatment period.

BMJ OPEN (2021)

Article Clinical Neurology

Tau immunotherapy is associated with glial responses in FTLD-tau

Boram Kim et al.

Summary: The study found that Gosuranemab treatment did not lead to clearance of neuropathologic FTLD-tau inclusions, but did induce changes including the presence of perivascular vesicular astrocytes (PVA) with tau accumulation within lysosomes. These results suggest that Gosuranemab may be associated with a glial response involving tau accumulation within astrocytic lysosomes.

ACTA NEUROPATHOLOGICA (2021)

Article Biochemistry & Molecular Biology

Reducing acetylated tau is neuroprotective in brain injury

Min-Kyoo Shin et al.

Summary: Traumatic brain injury induces tau acetylation, leading to neurodegeneration and neurobehavioral impairment. Protecting mice from TBI can be achieved by blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1. Ac-tau may serve as a therapeutic target and potential blood biomarker of TBI.
Article Biochemistry & Molecular Biology

Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome

Mathieu Bourdenx et al.

Summary: This study reveals that loss of neuronal CMA leads to altered neuronal function, changes in the neuronal proteome, and proteotoxicity, while enhancing CMA can ameliorate pathology in Alzheimer's disease mouse models. Functional CMA is essential for maintaining neuronal proteostasis and protecting against neurodegenerative diseases.
Article Multidisciplinary Sciences

TSC1 loss increases risk for tauopathy by inducing tau acetylation and preventing tau clearance via chaperone-mediated autophagy

Carolina Alquezar et al.

Summary: Genetic variants in TSC1 decrease TSC1/hamartin levels, leading to tau accumulation and susceptibility to tauopathies, by modulating p300 and SIRT1 enzymes, tau levels can be restored.

SCIENCE ADVANCES (2021)

Article Biochemistry & Molecular Biology

LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation

Green Ahn et al.

Summary: Selective protein degradation platforms such as LYTACs provide new opportunities for therapeutic development and biological research. By targeting specific lysosome receptors in a cell-type-specific manner, these LYTACs can efficiently degrade extracellular proteins and hold promise for cell-type-restricted protein degradation strategies.

NATURE CHEMICAL BIOLOGY (2021)

Article Multidisciplinary Sciences

Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice

Benjamin Caballero et al.

Summary: The study shows that acetylation of tau protein reduces its degradation through chaperone-mediated autophagy, leading to rerouting to other autophagic pathways and increased extracellular release of tau.

NATURE COMMUNICATIONS (2021)

Article Pharmacology & Pharmacy

Current Status of Clinical Trials on Tau Immunotherapies

Changyi Ji et al.

Summary: Tau immunotherapies have progressed from proof-of-concept studies to multiple clinical trials, with some focusing on targeting intracellular tau while others target extracellular tau. There is no consensus on the ideal tau pool to target, or the efficacy of different epitopes and antibody isotypes. Most trials are in early stages with no major adverse effects reported, but some have been discontinued due to poor pharmacokinetics or lack of efficacy. Decision makers should consider targeting both extracellular and intracellular tau to potentially improve success rates.
Review Neurosciences

Don't Phos Over Tau: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer's disease and other tauopathies

Yuxing Xia et al.

Summary: Phosphorylation is a common post-translational modification in tau protein isolated from Alzheimer's disease patients, with therapeutic approaches targeting phosphorylated tau showing promise in slowing hyperphosphorylation and aggregation. The identification and monitoring of phosphorylated tau could serve as disease-specific biomarkers, aiding in clinical diagnosis and progression monitoring.

MOLECULAR NEURODEGENERATION (2021)

Review Neurosciences

Cellular and pathological heterogeneity of primary tauopathies

Dah-eun Chloe Chung et al.

Summary: Pathological tau can promote aggregation and propagation of endogenous tau, but tauopathies differ in terms of predominant tau isoforms and selective vulnerability of brain regions. Variability in tau pathology in neuronal and glial cells challenges our understanding of tauopathies and the development of therapeutic strategies.

MOLECULAR NEURODEGENERATION (2021)

Editorial Material Biochemistry & Molecular Biology

Tau-targeting antibody therapies: too late, wrong epitope or wrong target?

Edwin Jabbari et al.

Summary: Two phase 2 studies of N-terminal tau-targeting antibody therapy did not demonstrate clinical efficacy in progressive supranuclear palsy, despite evidence of target engagement.

NATURE MEDICINE (2021)

Article Biochemistry & Molecular Biology

Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial

Tien Dam et al.

Summary: In the conducted study, treatment with the anti-tau antibody gosuranemab for progressive supranuclear palsy did not show clinical benefit. Gosuranemab did not demonstrate efficacy compared to placebo in terms of PSP Rating Scale score and secondary endpoints. The study indicates that N-terminal tau neutralization does not result in clinical efficacy.

NATURE MEDICINE (2021)

Article Cell Biology

Cis P-tau underlies vascular contribution to cognitive impairment and dementia and can be effectively targeted by immunotherapy in mice

Chenxi Qiu et al.

Summary: The study demonstrates that cis P-tau may play a significant role in mediating VCID and AD, and targeting it with antibodies could be beneficial for early diagnosis, prevention, and treatment of cognitive impairment and dementia. The research also shows that targeting cis P-tau in VCID mice effectively rescues neurodegeneration and cognitive impairment, and prevents progression of AD-like neurodegeneration and memory loss. Additionally, single-cell RNA sequencing revealed that cis-targeted immunotherapy can reverse diverse transcriptomic changes in VCID mice resembling those seen in AD patients.

SCIENCE TRANSLATIONAL MEDICINE (2021)

Article Geriatrics & Gerontology

Association of Tau Pathology With Clinical Symptoms in the Subfields of Hippocampal Formation

Xinting Ge et al.

Summary: The study aimed to investigate the relationship between clinical symptoms and tauopathy in hippocampal subfields under different amyloid statuses. Results demonstrated that individuals in the amyloid positive group showed more impairment and significant changes in hippocampal subfields compared to the amyloid negative group. Tau pathology in the hippocampus was associated with memory deficits and behavioral impairments, especially within the amyloid positive group.

FRONTIERS IN AGING NEUROSCIENCE (2021)

Article Neurosciences

Phosphorylation and O-GlcNAcylation of the PHF-1 Epitope of Tau Protein Induce Local Conformational Changes of the C-Terminus and Modulate Tau Self-Assembly Into Fibrillar Aggregates

Francois-Xavier Cantrelle et al.

Summary: Phosphorylation of Tau protein plays a critical role in the aggregation process observed in Alzheimer's disease brains. Recent research has highlighted the regulatory role of O-GlcNAcylation in modulating Tau phosphorylation and aggregation. Results showed that O-GlcNAcylation reduces phosphorylation of PHF-1 epitope, which is hyperphosphorylated in AD brains, and impacts the rate of fibrillar assembly in in-vitro assays.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2021)

Article Genetics & Heredity

Administration of AAV-Alpha Synuclein NAC Antibody Improves Locomotor Behavior in Rats Overexpressing Alpha Synuclein

Yun-Hsiang Chen et al.

Summary: The study demonstrates that intervention with AAV-NAC32 on alpha-Synuclein in animals can improve PD-like symptoms, including reducing bradykinesia and restoring tyrosine hydroxylase loss. This research provides hope for this intervention technique as a potential therapeutic candidate for PD.
Article Biochemistry & Molecular Biology

A novel dephosphorylation targeting chimera selectively promoting tau removal in tauopathies

Jie Zheng et al.

Summary: The novel DEPTAC designed and synthesized in this study effectively dephosphorylates tau at AD-associated sites and prevents its accumulation. DEPTAC improves microtubule assembly, synaptic plasticity, and hippocampus-dependent learning and memory, providing a new strategy for the targeted therapy of AD and related tauopathies.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

Article Cell Biology

ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer's disease

Petr Novak et al.

Summary: The study demonstrates that AADvac1, a tau vaccine against Alzheimer's disease, is safe and immunogenic, but no significant clinical efficacy was observed in the whole study sample.

NATURE AGING (2021)

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CSF tau microtubule binding region identifies tau tangle and clinical stages of Alzheimer's disease

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Summary: The study analyzed MTBR-tau species in CSF and found that tau species containing the upstream region of MTBR were highly correlated with tau PET and cognitive assessments in Alzheimer's disease, suggesting they could serve as biomarkers for staging Alzheimer's disease and tracking tau-directed therapeutics development.
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A novel small-molecule PROTAC selectively promotes tau clearance to improve cognitive functions in Alzheimer-like models

Weijin Wang et al.

Summary: The novel small-molecule PROTAC, C004019, showed promising results in selectively promoting tau protein clearance and improving synaptic and cognitive functions.

THERANOSTICS (2021)

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JOURNAL OF EXPERIMENTAL MEDICINE (2020)

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Primary Tau Pathology, Not Copathology, Correlates With Clinical Symptoms in PSP and CBD

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ACTA NEUROPATHOLOGICA COMMUNICATIONS (2020)

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Neuronally expressed anti-tau scFv prevents tauopathy-induced phenotypes in Drosophila models

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CURRENT OPINION IN STRUCTURAL BIOLOGY (2020)

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Insoluble Tau From Human FTDP-17 Cases Exhibit Unique Transmission Properties In Vivo

Sarah A. Weitzman et al.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2020)

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Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer's Disease

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NEUROBIOLOGY OF DISEASE (2020)

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Pharmacological Modulators of Tau Aggregation and Spreading

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BRAIN SCIENCES (2020)

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FRONTIERS IN NEUROLOGY (2020)

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CELL CHEMICAL BIOLOGY (2020)

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Open-Label Phase 1 Futility Studies of Salsalate and Young Plasma in Progressive Supranuclear Palsy

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MOVEMENT DISORDERS CLINICAL PRACTICE (2020)

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Michael W. Handlogten et al.

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Microglial activation in early Alzheimer trajectory is associated with higher gray matter volume

Grazia Daniela Femminella et al.

NEUROLOGY (2019)

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A walk through tau therapeutic strategies

Santosh Jadhav et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2019)

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Involvement of Oligodendrocytes in Tau Seeding and Spreading in Tauopathies

Isidro Ferrer et al.

FRONTIERS IN AGING NEUROSCIENCE (2019)

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Phospho-Tau Changes in the Human CA1 During Alzheimer's Disease Progression

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JOURNAL OF ALZHEIMERS DISEASE (2019)

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Neuronal FcγRI mediates acute and chronic joint pain

Li Wang et al.

JOURNAL OF CLINICAL INVESTIGATION (2019)

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Compromised function of the ESCRT pathway promotes endolysosomal escape of tau seeds and propagation of tau aggregation

John J. Chen et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

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MOLECULAR NEURODEGENERATION (2019)

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Autoantibodies to synapsin I sequestrate synapsin I and alter synaptic function

Anna Rocchi et al.

CELL DEATH & DISEASE (2019)

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cis pT231-Tau Drives Neurodegeneration in Bipolar Disorder

Roghayeh Naserkhaki et al.

ACS CHEMICAL NEUROSCIENCE (2019)

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A critical appraisal of amyloid-βtargeting therapies for Alzheimer disease

Francesco Panza et al.

NATURE REVIEWS NEUROLOGY (2019)

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AUTACs: Cargo-Specific Degraders Using Selective Autophagy

Daiki Takahashi et al.

MOLECULAR CELL (2019)

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Regulation of Antigen Export to the Cytosol During Cross-Presentation

Marine Gros et al.

FRONTIERS IN IMMUNOLOGY (2019)

Review Genetics & Heredity

Antisense oligonucleotides

Daniel R. Scoles et al.

NEUROLOGY-GENETICS (2019)

Review Biochemistry & Molecular Biology

Protein phosphatase 2A and tau: an orchestrated 'Pas de Deux'

Goce Taleski et al.

FEBS LETTERS (2018)

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Mengchen Lu et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2018)

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Tau Proteolysis in the Pathogenesis of Tauopathies: Neurotoxic Fragments and Novel Biomarkers

James P. Quinn et al.

JOURNAL OF ALZHEIMERS DISEASE (2018)

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Tau-targeting therapies for Alzheimer disease

Erin E. Congdon et al.

NATURE REVIEWS NEUROLOGY (2018)

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Tau Kinetics in Neurons and the Human Central Nervous System

Chihiro Sato et al.

NEURON (2018)

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The Association of Tau With Mitochondrial Dysfunction in Alzheimer's Disease

Ying Cheng et al.

FRONTIERS IN NEUROSCIENCE (2018)

Review Immunology

Current Concepts of Antigen Cross-Presentation

Maria Embgenbroich et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Phosphorylation of different tau sites during progression of Alzheimer's disease

Joerg Neddens et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2018)

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Epitope determines efficacy of therapeutic anti-Tau antibodies in a functional assay with human Alzheimer Tau

Jean-Philippe Courade et al.

ACTA NEUROPATHOLOGICA (2018)

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Structures of filaments from Pick's disease reveal a novel tau protein fold

Benjamin Falcon et al.

NATURE (2018)

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Anti-tau conformational scFv MC1 antibody efficiently reduces pathological tau species in adult JNPL3 mice

Francesca Vitale et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2018)

Article Multidisciplinary Sciences

Aggregated SOD1 causes selective death of cultured human motor neurons

Chen Benkler et al.

SCIENTIFIC REPORTS (2018)

Article Cell Biology

Interplay of pathogenic forms of human tau with different autophagic pathways

Benjamin Caballero et al.

AGING CELL (2018)

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Curcumin Inhibits Tau Aggregation and Disintegrates Preformed Tau Filaments in vitro

Jitendra Subhash Rane et al.

JOURNAL OF ALZHEIMERS DISEASE (2017)

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AAV-mediated expression of anti-tau scFvs decreases tau accumulation in a mouse model of tauopathy

Christina Ising et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2017)

Review Neurosciences

Glial contributions to neurodegeneration in tauopathies

Cheryl E. G. Leyns et al.

MOLECULAR NEURODEGENERATION (2017)

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Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation

William A. McEwan et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2017)

Article Multidisciplinary Sciences

p62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis

Hyunjoo Cha-Molstad et al.

NATURE COMMUNICATIONS (2017)

Article Multidisciplinary Sciences

Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae

Onder Albayram et al.

NATURE COMMUNICATIONS (2017)

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Tau Oligomers: Cytotoxicity, Propagation, and Mitochondrial Damage

Scott S. Shafiei et al.

FRONTIERS IN AGING NEUROSCIENCE (2017)

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Characterization of TauC3 antibody and demonstration of its potential to block tau propagation

Samantha B. Nicholls et al.

PLOS ONE (2017)

Article Multidisciplinary Sciences

Prophylactic Active Tau Immunization Leads to Sustained Reduction in Both Tau and Amyloid-β Pathologies in 3xTg Mice

Hameetha Rajamohamedsait et al.

SCIENTIFIC REPORTS (2017)

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Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins

William P. Flavin et al.

ACTA NEUROPATHOLOGICA (2017)

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Waltraud Mair et al.

ANALYTICAL CHEMISTRY (2016)

Review Biochemistry & Molecular Biology

Potential mechanisms and implications for the formation of tau oligomeric strains

Julia E. Gerson et al.

CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY (2016)

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A Phase IIa Randomized Control Trial of VEL015 ( Sodium Selenate) in Mild-Moderate Alzheimer's Disease

Charles B. Malpas et al.

JOURNAL OF ALZHEIMERS DISEASE (2016)

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Tengfei Li et al.

JOURNAL OF CONTROLLED RELEASE (2016)

Article Medicine, Research & Experimental

Charge heterogeneity: Basic antibody charge variants with increased binding to Fc receptors

Beate Hintersteiner et al.

Article Geriatrics & Gerontology

Detecting tau in serum of transgenic animal models after tau immunotherapy treatment

Cristina d'Abramo et al.

NEUROBIOLOGY OF AGING (2016)

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Loss of Bin1 Promotes the Propagation of Tau Pathology

Sara Calafate et al.

CELL REPORTS (2016)

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Lipid peroxidation causes endosomal antigen release for cross-presentation

Ilse Dingjan et al.

SCIENTIFIC REPORTS (2016)

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Specific Knockdown of Endogenous Tau Protein by Peptide-Directed Ubiquitin-Proteasome Degradation

Ting-Ting Chu et al.

CELL CHEMICAL BIOLOGY (2016)

Article Biochemistry & Molecular Biology

Distinct Therapeutic Mechanisms of Tau Antibodies PROMOTING MICROGLIAL CLEARANCE VERSUS BLOCKING NEURONAL UPTAKE

Kristen E. Funk et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2015)

Article Biochemistry & Molecular Biology

Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits

Sang-Won Min et al.

NATURE MEDICINE (2015)

Article Geriatrics & Gerontology

Human secreted tau increases amyloid-beta production

Jessica Bright et al.

NEUROBIOLOGY OF AGING (2015)

Article Multidisciplinary Sciences

Charge-mediated influence of the antibody variable domain on FcRn-dependent pharmacokinetics

Angela Schoch et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2015)

Article Neurosciences

Posttranslational modifications of α-tubulin in alzheimer disease

Fan Zhang et al.

TRANSLATIONAL NEURODEGENERATION (2015)

Article Neurosciences

Preventive methylene blue treatment preserves cognition in mice expressing full-length pro-aggregant human Tau

Katja Hochgraefe et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2015)

Article Clinical Neurology

Divergent CSF τ alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy

Dana Wagshal et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2015)

Article Clinical Neurology

Passive immunotherapy of tauopathy targeting pSer413-tau: a pilot study in mice

Tomohiro Umeda et al.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2015)

Review Biochemistry & Molecular Biology

The Role of Tau Oligomers in the Onset of Alzheimer's Disease Neuropathology

Maria del Carmen Cardenas-Aguayo et al.

ACS CHEMICAL NEUROSCIENCE (2014)

Article Clinical Neurology

Primary age-related tauopathy (PART): a common pathology associated with human aging

John F. Crary et al.

ACTA NEUROPATHOLOGICA (2014)

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Structure and Mechanism of Action of Tau Aggregation Inhibitors

Katryna Cisek et al.

CURRENT ALZHEIMER RESEARCH (2014)

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Estimation of polyclonal IgG4 hybrids in normal human serum

Elizabeth Young et al.

IMMUNOLOGY (2014)

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Antibody-Derived In Vivo Imaging of Tau Pathology

Senthilkumar Krishnaswamy et al.

JOURNAL OF NEUROSCIENCE (2014)

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Protein phosphatase 2A dysfunction in Alzheimer's disease

Jean-Marie Sontag et al.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2014)

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Repeated immunization of mice with phosphorylated-tau peptides causes neuroinflammation

Lea Rozenstein-Tsalkovich et al.

EXPERIMENTAL NEUROLOGY (2013)

Article Biochemistry & Molecular Biology

Two Novel Tau Antibodies Targeting the 396/404 Region Are Primarily Taken Up by Neurons and Reduce Tau Protein Pathology

Jiaping Gu et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2013)

Article Biochemistry & Molecular Biology

The constant region affects antigen binding of antibodies to DNA by altering secondary structure

Yumin Xia et al.

MOLECULAR IMMUNOLOGY (2013)

Review Clinical Neurology

Alzheimer disease therapy-moving from amyloid-β to tau

Ezio Giacobini et al.

NATURE REVIEWS NEUROLOGY (2013)

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Tau Passive Immunotherapy in Mutant P301L Mice: Antibody Affinity versus Specificity

Cristina d'Abramo et al.

PLOS ONE (2013)

Article Multidisciplinary Sciences

Brain homogenates from human tauopathies induce tau inclusions in mouse brain

Florence Clavaguera et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

Review Clinical Neurology

The importance of tau phosphorylation for neurodegenerative diseases

Wendy Noble et al.

FRONTIERS IN NEUROLOGY (2013)

Review Clinical Neurology

Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature

Peter T. Nelson et al.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2012)

Article Oncology

TPI-287, a New Taxane Family Member, Reduces the Brain Metastatic Colonization of Breast Cancer Cells

Daniel P. Fitzgerald et al.

MOLECULAR CANCER THERAPEUTICS (2012)

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The non-fluent/agrammatic variant of primary progressive aphasia

Murray Grossman

LANCET NEUROLOGY (2012)

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Hyperphosphorylation and Cleavage at D421 Enhance Tau Secretion

Vanessa Plouffe et al.

PLOS ONE (2012)

Article Multidisciplinary Sciences

Methylene Blue Reduced Abnormal Tau Accumulation in P301L Tau Transgenic Mice

Masato Hosokawa et al.

PLOS ONE (2012)

Article Multidisciplinary Sciences

Isotype modulates epitope specificity, affinity, and antiviral activities of anti-HIV-1 human broadly neutralizing 2F5 antibody

Daniela Tudor et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

Article Pathology

Reactive Glia not only Associates with Plaques but also Parallels Tangles in Alzheimer's Disease

Alberto Serrano-Pozo et al.

AMERICAN JOURNAL OF PATHOLOGY (2011)

Article Biochemistry & Molecular Biology

Sequence-independent Control of Peptide Conformation in Liposomal Vaccines for Targeting Protein Misfolding Diseases

David T. Hickman et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2011)

Article Clinical Neurology

Granulovacuolar degeneration (GVD) bodies of Alzheimer's disease (AD) resemble late-stage autophagic organelles

K. E. Funk et al.

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY (2011)

Review Neurosciences

Biomarkers in frontotemporal lobar degenerations-Progress and challenges

William T. Hu et al.

PROGRESS IN NEUROBIOLOGY (2011)

Letter Allergy

Evidence for neuronal expression of functional Fc (epsilon and gamma) receptors

Hanneke van der Kleij et al.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2010)

Article Clinical Neurology

Purkinje Cell Death After Uptake of Anti-Yo Antibodies in Cerebellar Slice Cultures

John E. Greenlee et al.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2010)

Article Neurosciences

Immunotherapy Targeting Pathological Tau Prevents Cognitive Decline in a New Tangle Mouse Model

Allal Boutajangout et al.

JOURNAL OF NEUROSCIENCE (2010)

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Sodium selenate mitigates tau pathology, neurodegeneration, and functional deficits in Alzheimer's disease models

Janet van Eersel et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2010)

Article Biochemistry & Molecular Biology

Improving the solubility of anti-LINGO-1 monoclonal antibody Li33 by isotype switching and targeted mutagenesis

R. Blake Pepinsky et al.

PROTEIN SCIENCE (2010)

Article Biochemistry & Molecular Biology

Minocycline reduces the development of abnormal tau species in models of Alzheimer's disease

Wendy Noble et al.

FASEB JOURNAL (2009)

Article Biochemistry & Molecular Biology

Tau - an inhibitor of deacetylase HDAC6 function

Mar Perez et al.

JOURNAL OF NEUROCHEMISTRY (2009)

Article Biotechnology & Applied Microbiology

Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo

Aran F. Labrijn et al.

NATURE BIOTECHNOLOGY (2009)

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Amyloid activates GSK-3β to aggravate neuronal tauopathy in bigenic mice

Dick Terwel et al.

AMERICAN JOURNAL OF PATHOLOGY (2008)

Editorial Material Pharmacology & Pharmacy

Curcumin as Curecumin:: From kitchen to clinic

Ajay Goel et al.

BIOCHEMICAL PHARMACOLOGY (2008)

Article Geriatrics & Gerontology

Cathepsin D expression is decreased in Alzheimer's disease fibroblasts

Lorena Urbanelli et al.

NEUROBIOLOGY OF AGING (2008)

Article Clinical Neurology

Protective effects of NSAIDs on the development of Alzheimer disease

Steven C. Vlad et al.

NEUROLOGY (2008)

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Protein S-guanylation by the biological signal 8-nitroguanosine 3′,5′-cyclic monophosphate

Tomohiro Sawa et al.

NATURE CHEMICAL BIOLOGY (2007)

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CD3 and immunoglobulin G Fc receptor regulate cerebellar functions

Kazuhiro Nakamura et al.

MOLECULAR AND CELLULAR BIOLOGY (2007)

Article Biochemistry & Molecular Biology

beta-amyloid peptide toxicity in organotypic hippocampal slice culture involves Akt/PKB, GSK-3 beta, and PTEN

Melissa Nassif et al.

NEUROCHEMISTRY INTERNATIONAL (2007)

Review Biochemistry & Molecular Biology

Mannose 6-phosphate receptor targeting and its applications in human diseases

M. Gary-Bobo et al.

CURRENT MEDICINAL CHEMISTRY (2007)

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Tauopathy-like abnormalities and neurologic deficits in mice immunized with neuronal tau protein

Hanna Rosenmann et al.

ARCHIVES OF NEUROLOGY (2006)

Article Biochemistry & Molecular Biology

Involvement of I2PP2A in the abnormal hyperphosphorylation of tau and its reversal by Memantine

Muhammad Omar Chohan et al.

FEBS LETTERS (2006)

Article Clinical Neurology

Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer's disease

M Grossman et al.

ANNALS OF NEUROLOGY (2005)

Article Public, Environmental & Occupational Health

Meta-analysis of nonsteroidal antiinflammatory drug use and risk of dementia

AJM de Craen et al.

AMERICAN JOURNAL OF EPIDEMIOLOGY (2005)

Article Multidisciplinary Sciences

O-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer's disease

F Liu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2004)

Article Biotechnology & Applied Microbiology

A human single-chain Fv intrabody blocks aberrant cellular effects of overexpressed α-synuclein

C Zhou et al.

MOLECULAR THERAPY (2004)

Article Biochemistry & Molecular Biology

Direct action of immunoglobulin G on primary sensory neurons through Fc gamma receptor I

T Andoh et al.

FASEB JOURNAL (2004)

Review Cell Biology

Mannose 6-phosphate receptors: New twists in the tale

P Ghosh et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2003)

Article Geriatrics & Gerontology

Clogging of axons by tau, inhibition of axonal traffic and starvation of synapses

EM Mandelkow et al.

NEUROBIOLOGY OF AGING (2003)

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p35/Cdk5 pathway mediates soluble amyloid-β peptide-induced tau phosphorylation in vitro

T Town et al.

JOURNAL OF NEUROSCIENCE RESEARCH (2002)

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A survey of Cdk5 activator p35 and p25 levels in Alzheimer's disease brains

HC Tseng et al.

FEBS LETTERS (2002)

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Impaired proteasome function in Alzheimer's disease

JN Keller et al.

JOURNAL OF NEUROCHEMISTRY (2000)