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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

Published on: January 2, 2015

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Cerebral hypoperfusion reduces tau accumulation

Ghupurjan Gheni1, Mitsuru Shinohara1,2, Masami Masuda-Suzukake3

  • 1Department of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, 474-8511, Japan.

Annals of Clinical and Translational Neurology
|December 2, 2024
PubMed

Insights

Cerebrovascular diseases like stroke may reduce Alzheimer's disease (AD) tau pathology. Chronic cerebral hypoperfusion lowers tau accumulation, potentially via enhanced microglial activity and cathepsin D, offering insights into multimorbidity.

Area of Science:

  • Neuroscience
  • Neuropathology
  • Gerontology

Background:

  • Alzheimer's disease (AD) frequently co-occurs with cerebrovascular diseases.
  • The specific impact of cerebrovascular conditions on AD pathology is not well-defined.

Purpose of the Study:

  • To investigate the relationship between cerebrovascular diseases and Alzheimer's disease pathology.
  • To elucidate the mechanisms by which cerebral hypoperfusion influences tau accumulation.

Main Methods:

  • Analysis of clinical and neuropathological data from the National Alzheimer's Coordinating Center (NACC) database.
  • Utilized a mouse model with bilateral common carotid artery stenosis and tau seed injection to study chronic cerebral hypoperfusion's effects on tau pathology in neurons, astrocytes, microglia, and oligodendrocytes.

Main Results:

  • Clinical stroke history and lacunar infarcts correlated with reduced neurofibrillary tangle pathology in human data.
  • Cerebral hypoperfusion in the animal model decreased tau pathology across multiple cell types.
  • Activated astrocytes and microglia were observed under conditions of tau pathology and hypoperfusion.
  • Lysosomal enzyme cathepsin D levels increased with cerebral hypoperfusion.

Conclusions:

  • Cerebral hypoperfusion appears to reduce tau accumulation by increasing microglial phagocytosis of tau and enhancing degradation via cathepsin D.
  • Findings illuminate the interplay between tau pathology and cerebrovascular diseases in older adults with multiple health conditions.
Abstract

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