Limbic-predominant age-related TDP-43 proteinopathy (LATE-NC) is associated with abundant TMEM106B pathology

Article Clinical Neurology

Accumulation of TMEM106B C-terminal fragments in neurodegenerative disease and aging

Jolien Perneel et al.

Summary: Several studies using cryo-EM techniques have found novel protein filaments composed of a CTF of TMEM106B in brain tissue with neurodegenerative conditions and aging. TMEM106B variants are known to affect the risk and presentation of neurodegenerative diseases. TMEM106B CTF accumulation was found to be a common age-related phenomenon, suggesting lysosomal dysfunction.

ACTA NEUROPATHOLOGICA (2023)

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Article Biochemistry & Molecular Biology

Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases

Andrew Chang et al.

Summary: This study demonstrates the presence of amyloid fibrils composed of TMEM106B in various neurodegenerative diseases, suggesting a potential shared fibrillization pathway.

CELL (2022)

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Article Multidisciplinary Sciences

Age-dependent formation of TMEM106B amyloid filaments in human brains

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.

NATURE (2022)

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Article Multidisciplinary Sciences

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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Review Clinical Neurology

Identification of TMEM106B amyloid fibrils provides an updated view of TMEM106B biology in health and disease

Jolien Perneel et al.

Summary: TMEM106B is a gene associated with the risk of neurodegenerative diseases and healthy aging. It is involved in lysosomal function and the formation of amyloid fibrils. Research on TMEM106B provides a new perspective on brain disorders and brain health.

ACTA NEUROPATHOLOGICA (2022)

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Review Clinical Neurology

Physiological and pathological functions of TMEM106B: a gene associated with brain aging and multiple brain disorders

Tuancheng Feng et al.

Summary: TMEM106B, a lysosome membrane protein, is associated with brain aging, neurodegenerative diseases, and regulates various aspects of lysosomal function. Both deficiency and alterations in TMEM106B levels are linked to lysosomal abnormalities and brain disorders.

ACTA NEUROPATHOLOGICA (2021)

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Article Neurosciences

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

Adam J. Dugan et al.

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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Review Clinical Neurology