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Limbic-Predominant Age-Related TDP-43 Encephalopathy: LATE-Breaking Updates in Clinicopathologic Features and Biomarkers

CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS (2022)

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Distinct characteristics of limbic-predominant age-related TDP-43 encephalopathy in Lewy body disease

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Summary: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is characterized by the accumulation of TAR-DNA-binding protein 43 (TDP-43) aggregates in older adults and coexists with Lewy body disease (LBD) and Alzheimer's disease (AD). Pathological and genetic characteristics of LATE in LBD (LATE-LBD) differ from LATE-AD, with associations to patient profiles and cognitive impairment. The distribution of LATE neuropathological changes and genetic risk factors also vary between LATE-LBD and LATE-AD.

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NATURE (2022)

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Limbic-Predominant Age-Related TDP-43 Encephalopathy Medical and Pathologic Factors Associated With Comorbid Hippocampal Sclerosis

Kathryn M. Gauthreaux et al.

Summary: Limbic-predominant age-related Tar DNA binding protein 43 (TDP-43) encephalopathy neuropathologic change (LATE-NC) is strongly associated with cognitive impairment. This study found that LATE-NC patients with hippocampal sclerosis (HS) pathology may have worse cognitive status and more severe impairments in memory and orientation. Additionally, the presence of comorbid HS pathology is associated with more widespread TDP-43 proteinopathy and more severe non-beta-amyloid vessel wall pathologies.

NEUROLOGY (2022)

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TDP-43-associated atrophy in brains with and without frontotemporal lobar degeneration

Marina Buciuc et al.

Summary: The study found differences and similarities in longitudinal brain volume loss between FTLD-TDP and non-FTLD TDP-43, with faster atrophy rates in certain brain regions for FTLD-TDP and faster hippocampal atrophy rates in AD-TDP type-a.

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White matter damage due to vascular, tau, and TDP-43 pathologies and its relevance to cognition

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Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases

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Multimarker synaptic protein cerebrospinal fluid panels reflect TDP-43 pathology and cognitive performance in a pathological cohort of frontotemporal lobar degeneration

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Manuel Schweighauser et al.

Summary: The study found that TMEM106B protein forms amyloid filaments in the brains of patients with various neurodegenerative diseases. The structures of TMEM106B filaments differ in different brain regions and do not show clear associations with specific diseases. The presence of TMEM106B filaments in the brains of older individuals suggests an age-dependent formation pattern, which is not observed in younger individuals with normal neurology.

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Amyloid fibrils in FTLD-TDP are composed of TMEM106B and not TDP-43

Yi Xiao Jiang et al.

Summary: This study found that amyloid fibrils in FTLD-TDP patients are formed by TMEM106B protein rather than TDP-43 protein. In addition, abundant non-fibrillar aggregated TDP-43 protein was observed.

NATURE (2022)

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Frequency of LATE neuropathologic change across the spectrum of Alzheimer's disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts

Peter T. Nelson et al.

Summary: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer's disease neuropathologic change (ADNC) are both associated with cognitive impairment in aging populations, with LATE-NC being present in approximately 40% of participants and more commonly in cases with poorer cognitive abilities.

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Blood TDP-43 Combined with Demographics Information Predicts Dementia Occurrence in Community Non-Dementia Elderly

Lin Sun et al.

Summary: In this study, it was found that blood TDP-43 levels were higher in subjects progressing from NC/MCI to dementia compared to stable NC/MCI group. A combination of baseline blood TDP-43 levels with demographics could predict dementia occurrence, while baseline blood levels of NfL were negatively associated with cognitive function at 7-year follow-up. Additionally, there was no relationship between CSF and blood levels of TDP-43, and the levels of TDP-43 in CSF were positively associated with the age of patients, especially in AD group.

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Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change and microvascular pathologies in community-dwelling older persons

Sonal Agrawal et al.

Summary: The study found that LATE-NC is commonly associated with microvascular pathologies, particularly posterior watershed arteriolosclerosis. This suggests that small vessel disease pathology may play a role in the development of LATE-NC in the aging brain.

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The association of Lewy bodies with limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes and their role in cognition and Alzheimer's dementia in older persons

Sonal Agrawal et al.

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ACTA NEUROPATHOLOGICA COMMUNICATIONS (2021)

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Distinct brain-derived TDP-43 strains from FTLD-TDP subtypes induce diverse morphological TDP-43 aggregates and spreading patterns in vitro and in vivo

Silvia Porta et al.

Summary: This study demonstrates the presence of distinct TDP-43 strains in the brains of different FTLD-TDP subtypes with specific seeding and spreading properties in experimental animal models.

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Michael Tran Duong et al.

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FRONTIERS IN AGING NEUROSCIENCE (2021)

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A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

Douglas P. Wightman et al.

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TDP-43 and Phosphorylated TDP-43 Levels in Paired Plasma and CSF Samples in Amyotrophic Lateral Sclerosis

Yuting Ren et al.

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ACTA NEUROPATHOLOGICA COMMUNICATIONS (2021)

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Analysis of genes (TMEM106B, GRN, ABCC9, KCNMB2, and APOE) implicated in risk for LATE-NC and hippocampal sclerosis provides pathogenetic insights: a retrospective genetic association study

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Summary: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is one of the most common subtypes of TDP-43 proteinopathy, often co-occurring with hippocampal sclerosis (HS) pathology, and showing associations with specific genetic variants. Through analyzing the genetic associations with HS, LATE-NC, and Alzheimer's pathologies, significant gene-based associations were found, offering new insights into the differential effects of risk alleles on LATE-NC and HS.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2021)

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TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease

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ANNALS OF NEUROLOGY (2007)

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TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2006)

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Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

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