4.6 Review

ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer's Disease

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Genetics & Heredity

Unraveling the Gordian knot: genetics and the troubled road to effective therapeutics for Alzheimer's disease

Linda L. Restifo

Summary: In the late 20th century, research on the molecular pathology of Alzheimer's disease led to the identification of major protein components and the amyloid-cascade hypothesis. However, a series of failed clinical trials in the past decade raised questions about the effectiveness of targeting amyloid for therapeutics. The focus on early-onset familial forms of the disease and the overlook of late-onset forms and tangles led to inaccurate diagnostic criteria and ineffective mouse models. Collaboration between geneticists and neuroscientists is needed to establish valid models and understand the pathogenesis of Alzheimer's.

GENETICS (2022)

Article Clinical Neurology

Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease

Stephen Salloway et al.

Summary: The EMERGE and ENGAGE phase 3 trials provided data on ARIA associated with aducanumab treatment in patients with Alzheimer's disease. A high rate of ARIA was observed, with ARIA-edema being the most common adverse event. Some patients in the aducanumab group experienced associated symptoms, with headache being the most common.

JAMA NEUROLOGY (2022)

Article Pharmacology & Pharmacy

Novel strategies for the fight of Alzheimer's disease targeting amyloid-β protein

Yang Xie et al.

Summary: This review discusses the current pharmacotherapy of AD targeting A beta, presenting recent clinical trial results and emerging anti-amyloid AD therapies based on recent studies. It also addresses some of the current challenges and novel strategies for preventing AD.

JOURNAL OF DRUG TARGETING (2022)

Article Clinical Neurology

The Ups and Downs of Amyloid in Alzheimer's

E. Siemers et al.

JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE (2022)

Review Clinical Neurology

The Development of Pharmacological Therapies for Alzheimer's Disease

Ping Lin et al.

Summary: Alzheimer's disease is a progressive neurodegenerative disorder without a cure. There is a growing need for more promising therapies due to the increasing elderly population worldwide. Recent efforts in clinical trials have focused on disease modification and symptomatic treatment, with varying results reported. The outcome of these trials and mechanisms of therapeutic agents are critical for guiding future drug development strategies.

NEUROLOGY AND THERAPY (2021)

Review Biology

Critical thinking on amyloid-beta-targeted therapy: challenges and perspectives

Bin-lu Sun et al.

Summary: The therapeutic strategy for Alzheimer's disease needs to be re-evaluated, with a focus on not only targeting amyloid-beta, but also other important pathological events as treatment targets. Tertiary prevention strategies are necessary for successful management of the complex and dynamic pathogenesis of Alzheimer's disease.

SCIENCE CHINA-LIFE SCIENCES (2021)

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)

Review Neurosciences

Therapeutic Strategies Targeting Amyloid-beta Receptors and Transporters in Alzheimer's Disease

Kejing Lao et al.

Summary: Alzheimer's disease is a chronic neurodegenerative disease with heavy social and economic costs. Amyloid-beta has been identified as a major factor in AD progression, causing neurotoxicity through interaction with membrane receptors. Targeting A beta receptors and transporters may be a potential approach for developing AD therapies in the future.

JOURNAL OF ALZHEIMERS DISEASE (2021)

Article Clinical Neurology

The Alzheimer's disease drug development landscape

Pieter van Bokhoven et al.

Summary: In the last 15 years, the diagnosis of Alzheimer's disease (AD) has shifted from syndromal to a biomarker construct based on pathological hallmarks. Genetic risk factors for AD have been identified, providing insight into the molecular basis of the disease. The AD drug development pipeline is diversifying in terms of targets and treatment modalities, with amyloid-targeting therapies remaining a prominent avenue of development.

ALZHEIMERS RESEARCH & THERAPY (2021)

Editorial Material Medicine, General & Internal

Evaluation of Aducanumab for Alzheimer Disease Scientific Evidence and Regulatory Review Involving Efficacy, Safety, and Futility

G. Caleb Alexander et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

Article Clinical Neurology

A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Aβ protofibril antibody

Chad J. Swanson et al.

Summary: BAN2401-G000-201 trial aimed to establish the effective dose and observe the treatment effect. While not meeting the primary endpoint at 12 months, results at 18 months demonstrated reduction in brain amyloid and improvement across multiple clinical and biomarker endpoints.

ALZHEIMERS RESEARCH & THERAPY (2021)

Editorial Material Clinical Neurology

Aducanumab produced a clinically meaningful benefit in association with amyloid lowering

Jeffrey Cummings et al.

ALZHEIMERS RESEARCH & THERAPY (2021)

Review Cell Biology

Effects of monoclonal antibodies against amyloid-β on clinical and biomarker outcomes and adverse event risks: A systematic review and meta-analysis of phase III RCTs in Alzheimer's disease

Konstantinos Avgerinos et al.

Summary: Monoclonal antibodies targeting A beta have shown small clinical improvements and large biomarker improvements in Alzheimer's disease patients. However, they also increase the risk of adverse events such as ARIA.

AGEING RESEARCH REVIEWS (2021)

Review Clinical Neurology

Critical Appraisal of Amyloid Lowering Agents in AD

Boris Decourt et al.

Summary: According to the amyloid cascade hypothesis, removing amyloid beta (A beta) is believed to cure Alzheimer's disease (AD), but current clinical trials lack definitive efficacy. Therefore, research has shifted focus towards immunotherapy, particularly monoclonal antibody therapies targeting A beta plaques. This approach offers potential for treating different stages of AD and may provide valuable insights into the trajectory of drug development for neurodegenerative diseases.

CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS (2021)

Article Ethics

Alzheimer's and Aducanumab: Unjust Profits and False Hopes

Leonard M. Fleck

Summary: The accelerated approval of aducanumab by the U.S. Food and Drug Administration for mild Alzheimer's on June 7, 2021, has sparked significant medical, scientific, and ethical controversy. Despite reducing beta-amyloid, the approval goes against the nearly unanimous judgment of the FDA's Advisory Committee due to limited reliable evidence of significant benefit. The approval has raised three major ethical concerns: unjust utilization of Medicare resources, ethical pressure on physicians to provide the drug to patients, and the generation of false hopes among patients.

HASTINGS CENTER REPORT (2021)

Review Biochemistry & Molecular Biology

Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer's Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression

Martin Tolar et al.

Summary: Research shows that inhibiting the toxicity of Aβ oligomers is an effective approach to slow or stop the progression of Alzheimer's disease, with drugs targeting other Aβ species failing to show clinical effects, while those with the APOE4 allele are more likely to benefit.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Review Biochemistry & Molecular Biology

Novel Therapeutic Approaches for Alzheimer's Disease: An Updated Review

Tien-Wei Yu et al.

Summary: Alzheimer's disease is a progressive neurodegenerative disease that presents a heavy burden on families and society. Current treatments are not effective, prompting the urgent need for novel therapeutic approaches to address the complex mechanisms of the disease. Potential interventions include drug repositioning and non-pharmacological treatments like repetitive transcranial magnetic stimulation and transcranial direct current stimulation.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Editorial Material Medicine, General & Internal

Approval of Aducanumab for Alzheimer Disease-the FDA's Perspective

Billy Dunn et al.

JAMA INTERNAL MEDICINE (2021)

Article Clinical Neurology

Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging

S. L. Lowe et al.

Summary: Donanemab, administered in single or multiple doses, demonstrated rapid, robust, and sustained reductions in brain amyloid plaque up to 72 weeks, despite detection of treatment-emergent antidrug antibodies in most patients. Amyloid-related imaging abnormalities were the most common treatment-emergent events observed.

JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE (2021)

Article Clinical Neurology

Aducanumab: Appropriate Use Recommendations

J. Cummings et al.

Summary: Aducanumab has been approved for the treatment of Alzheimer's disease by the FDA. It is recommended for use in patients with early AD, with dosage titration to maximize efficacy and monitoring for amyloid-related imaging abnormalities. Patient-centered informed decision-making is emphasized for clear communication on therapy expectations, risks, and benefits.

JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE (2021)

Article Clinical Neurology

2021 Alzheimer's disease facts and figures

[Anonymous]

Summary: Alzheimer's disease has a significant impact on individuals and society as a whole, with a large number of patients in the United States and a potential for continued growth in the future. The value of unpaid caregivers has increased despite a decline in their numbers, and healthcare costs are on the rise. Racial and ethnic disparities in healthcare persist, highlighting the need for greater diversity in dementia care workforce and clinical trials.

ALZHEIMERS & DEMENTIA (2021)

Article Clinical Neurology

Thirty-Six-Month Amyloid Positron Emission Tomography Results Show Continued Reduction in Amyloid Burden with Subcutaneous Gantenerumab

Gregory Klein et al.

Summary: The study demonstrates that prolonged treatment with high-dose gantenerumab can reduce amyloid plaque levels below the positivity threshold in patients with early to moderate Alzheimer's disease, showing continued reduction in amyloid plaque removal over time. Ongoing Phase III trials will evaluate the potential clinical benefits of gantenerumab-induced amyloid lowering in early-stage Alzheimer's disease patients.

JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE (2021)

Article Clinical Neurology

Lanabecestat: Neuroimaging results in early symptomatic Alzheimer's disease

Jennifer A. Zimmer et al.

Summary: Two studies found that lanabecestat can reduce Aβ neuritic plaque burden, but did not have an impact on aggregated tau neurofibrillary tangle burden, cerebral metabolism, and brain volume, instead causing reductions in brain volume. Correlations between imaging markers and cognitive assessments may assist in future study designs.

ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS (2021)

Editorial Material Geriatrics & Gerontology

WHO's global action plan on the public health response to dementia: some challenges and opportunities

Suzanne Cahill

AGING & MENTAL HEALTH (2020)

Review Biochemistry & Molecular Biology

APP Osaka Mutation in Familial Alzheimer's Disease-Its Discovery, Phenotypes, and Mechanism of Recessive Inheritance

Takami Tomiyama et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Review Biochemistry & Molecular Biology

A mechanistic hypothesis for the impairment of synaptic plasticity by soluble Aβ oligomers from Alzheimer's brain

Shaomin Li et al.

JOURNAL OF NEUROCHEMISTRY (2020)

Review Biochemistry & Molecular Biology

What works and what does not work in Alzheimer's disease? From interventions on risk factors to anti-amyloid trials

Szofia Bullain et al.

JOURNAL OF NEUROCHEMISTRY (2020)

Article Clinical Neurology

Cognitive outcomes in trials of two BACE inhibitors in Alzheimer's disease

Alette M. Wessels et al.

ALZHEIMERS & DEMENTIA (2020)

Review Neurosciences

Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer's disease

Tiantian Guo et al.

MOLECULAR NEURODEGENERATION (2020)

Editorial Material Neurosciences

Amyloid Hypothesis: The Emperor's New Clothes?

Poul F. Hoilund-Carlsen et al.

JOURNAL OF ALZHEIMERS DISEASE (2020)

Article Biochemistry & Molecular Biology

Systematic and standardized comparison of reported amyloid- receptors for sufficiency, affinity, and Alzheimer's disease relevance

Levi M. Smith et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

Review Clinical Neurology

Amyloid β oligomers (AβOs) in Alzheimer's disease

Barbara Mroczko et al.

JOURNAL OF NEURAL TRANSMISSION (2018)

Review Neurosciences

The Amyloid-beta Oligomer Hypothesis: Beginning of the Third Decade

Erika N. Cline et al.

JOURNAL OF ALZHEIMERS DISEASE (2018)

Editorial Material Multidisciplinary Sciences

THE AMYLOID HYPOTHESIS ON TRAIL

Simon Makin

NATURE (2018)

Editorial Material Pharmacology & Pharmacy

Amyloid in Alzheimer's Disease: Guilty Beyond Reasonable Doubt?

Christian Behl

TRENDS IN PHARMACOLOGICAL SCIENCES (2017)

Article Clinical Neurology

A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease

Susanne Ostrowitzki et al.

ALZHEIMERS RESEARCH & THERAPY (2017)

Article Neurosciences

Non-Fibrillar Oligomeric Amyloid-beta within Synapses

Eleanor K. Pickett et al.

JOURNAL OF ALZHEIMERS DISEASE (2016)

Article Multidisciplinary Sciences

The antibody aducanumab reduces Aβ plaques in Alzheimer's disease

Jeff Sevigny et al.

NATURE (2016)

Article Clinical Neurology

Safety and tolerability of BAN2401-a clinical study in Alzheimer's disease with a protofibril selective Aβ antibody

Veronika Logovinsky et al.

ALZHEIMERS RESEARCH & THERAPY (2016)

Review Clinical Neurology

Amyloid β oligomers in Alzheimer's disease pathogenesis, treatment, and diagnosis

Kirsten L. Viola et al.

ACTA NEUROPATHOLOGICA (2015)

Review Neurosciences

Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer's disease

Sergio T. Ferreira et al.

FRONTIERS IN CELLULAR NEUROSCIENCE (2015)

Review Clinical Neurology

Targeting the proper amyloid-beta neuronal toxins: a path forward for Alzheimer's disease immunotherapeutics

William F. Goure et al.

ALZHEIMERS RESEARCH & THERAPY (2014)

Review Neurosciences

Inconsistencies and Controversies Surrounding the Amyloid Hypothesis of Alzheimer's Disease

Gary P. Morris et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2014)

Article Neurosciences

Specific Uptake of an Amyloid-β Protofibril-Binding Antibody-Tracer in AβPP Transgenic Mouse Brain

Kristina Magnusson et al.

JOURNAL OF ALZHEIMERS DISEASE (2013)

Editorial Material Multidisciplinary Sciences

Promiscuous Alzheimer's Amyloid: Yet Another Partner

Iryna Benilova et al.

SCIENCE (2013)

Review Pharmacology & Pharmacy

The case for soluble Aβ oligomers as a drug target in Alzheimer's disease

Franz Hefti et al.

TRENDS IN PHARMACOLOGICAL SCIENCES (2013)

Review Clinical Neurology

Amyloid beta-protein oligomers and Alzheimer's disease

Eric Y. Hayden et al.

ALZHEIMERS RESEARCH & THERAPY (2013)

Article Biochemistry & Molecular Biology

Structural dynamics of the ΔE22 (Osaka) familial Alzheimer's disease-linked amyloid β-protein

Mohammed Inayathullah et al.

AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS (2011)

Article Geriatrics & Gerontology

Cognitive effects of cell-derived and synthetically derived Aβ oligomers

Miranda N. Reed et al.

NEUROBIOLOGY OF AGING (2011)

Review Behavioral Sciences

The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's disease

Sergio T. Ferreira et al.

NEUROBIOLOGY OF LEARNING AND MEMORY (2011)

Article Biochemistry & Molecular Biology

Structural conversion of neurotoxic amyloid-β1-42 oligomers to fibrils

Mahiuddin Ahmed et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2010)

Article Geriatrics & Gerontology

Anti-ADDL antibodies differentially block oligomer binding to hippocampal neurons

P. J. Shughrue et al.

NEUROBIOLOGY OF AGING (2010)

Article Neurosciences

Alzheimer's Disease Amyloid β-Protein and Synaptic Function

Tomas Ondrejcak et al.

NEUROMOLECULAR MEDICINE (2010)

Review Neurosciences

ADDLs and the signaling web that leads to Alzheimer's disease

Grant A. Krafft et al.

NEUROPHARMACOLOGY (2010)

Review Neurosciences

Alzheimer's disease: synaptic dysfunction and Aβ

Ganesh M. Shankar et al.

MOLECULAR NEURODEGENERATION (2009)

Article Medicine, Research & Experimental

IgG2m4, an engineered antibody isotype with reduced Fc function

Zhiqiang An et al.

Article Multidisciplinary Sciences

Oligomeric amyloid β associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques

Robert M. Koffie et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

Article Clinical Neurology

A new amyloid μ variant favoring oligomerization in Alzheimer's-type dementia

Takami Tomiyama et al.

ANNALS OF NEUROLOGY (2008)

Article Geriatrics & Gerontology

Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers

Fernanda G. De Felice et al.

NEUROBIOLOGY OF AGING (2008)

Article Biochemistry & Molecular Biology

Sensitive ELISA detection of amyloid-β protofibrils in biological samples

Hillevi Englund et al.

JOURNAL OF NEUROCHEMISTRY (2007)

Article Biochemistry & Molecular Biology

Accelerating amyloid-β fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models

Irene H. Cheng et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2007)

Review Biochemistry & Molecular Biology

A beta Oligomers - a decade of discovery

Dominic M. Walsh et al.

JOURNAL OF NEUROCHEMISTRY (2007)

Article Biochemistry & Molecular Biology

Solution state characterization of amyloid β-derived diffusible ligands

Robert W. Hepler et al.

BIOCHEMISTRY (2006)

Article Multidisciplinary Sciences

A specific amyloid-β protein assembly in the brain impairs memory

S Lesné et al.

NATURE (2006)

Article Biochemistry & Molecular Biology

Globular amyloid β-peptide1-42 oligomer -: a homogenous and stable neuropathological protein in Alzheimer's disease

S Barghorn et al.

JOURNAL OF NEUROCHEMISTRY (2005)

Article Neurosciences

Natural oligomers of the amyloid-protein specifically disrupt cognitive function

JP Cleary et al.

NATURE NEUROSCIENCE (2005)

Review Biochemistry & Molecular Biology

Oligomers in the brain: The emerging role of soluble protein aggregates in neurodegeneration

DM Walsh et al.

PROTEIN AND PEPTIDE LETTERS (2004)

Article Geriatrics & Gerontology

Mechanisms of the inhibitory effects of amyloid β-protein on synaptic plasticity

MJ Rowan et al.

EXPERIMENTAL GERONTOLOGY (2004)

Article Biochemistry & Molecular Biology

Self-assembly of Aβ1-42 into globular neurotoxins

BA Chromy et al.

BIOCHEMISTRY (2003)

Article Multidisciplinary Sciences

Alzheimer's disease-affected brain:: Presence of oligomeric Aβ ligands (ADDLs) suggests a molecular basis for reversible memory loss

YS Gong et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2003)

Article Biochemistry & Molecular Biology

Amyloid-β oligomers:: their production, toxicity and therapeutic inhibition

DM Walsh et al.

BIOCHEMICAL SOCIETY TRANSACTIONS (2002)

Article Biochemistry & Molecular Biology

Vaccination with soluble Aβ oligomers generates toxicity-neutralizing antibodies

MP Lambert et al.

JOURNAL OF NEUROCHEMISTRY (2001)

Review Neurosciences

Targeting small Aβ oligomers:: the solution to an Alzheimer's disease conundrum?

WL Klein et al.

TRENDS IN NEUROSCIENCES (2001)