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Updated: May 24, 2025

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Published on: September 28, 2019

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Mitochondrial accumulation and lysosomal dysfunction result in mitochondrial plaques in Alzheimer's disease

Xiuli Dan, Deborah L Croteau, Wenlong Liu

    Biorxiv : the Preprint Server for Biology
    |March 3, 2025
    PubMed

    Insights

    Researchers discovered mitochondrial plaques (MPs) in Alzheimer's disease (AD) brains. These MPs, containing accumulated mitochondria, represent a new pathological feature and potential therapeutic target for AD.

    Area of Science:

    • Neuroscience
    • Cell Biology
    • Pathology

    Background:

    • Dysfunctional mitophagy is implicated in Alzheimer's disease (AD) pathology.
    • Direct in vivo evidence and mechanistic insights into mitophagy dysfunction in AD are limited.

    Purpose of the Study:

    • To investigate the role of mitophagy in AD pathogenesis using a mouse model.
    • To identify and characterize novel pathological entities associated with AD.

    Main Methods:

    • Utilized a mitophagy reporter mouse model (APP/PSEN1/mt-Keima) for in vivo studies.
    • Examined brain tissues from AD and control mice, as well as human AD and healthy control brains.
    • Investigated mitochondrial accumulation, mitophagy, and lysosomal function.

    Main Results:

    • Identified "mitochondrial plaques" (MPs) composed of accumulated mitochondria in AD mouse and human brains, absent in controls.
    • Observed abnormal mitochondrial accumulation in dystrophic neurites due to defective mitophagy and impaired lysosomal function.
    • Found that MPs co-develop with amyloid plaques, forming mixed plaques.

    Conclusions:

    • Established mitochondrial plaques (MPs) as a novel pathological entity in Alzheimer's disease.
    • Demonstrated that MPs result from disrupted mitochondrial degradation and accumulation.
    • Highlighted MPs as a promising therapeutic target for AD intervention.

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