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Cardiac biomarkers are enzymes, proteins, and hormones released into the blood when cardiac cells are injured. They are powerful tools for triaging.
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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Preeti Sharma1

  • 1Centre for Brain Research, Bangalore, Karnataka, India.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

Cognitively resilient Alzheimer's disease (AD) patients maintain lysosomal integrity, while vulnerable patients show compromised lysosomes that spread tau pathology. Targeting lysosomal exocytosis may improve cognitive outcomes in AD.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Pathology

Background:

  • Tau pathology progression in Alzheimer's disease (AD) follows Braak staging and correlates with dementia severity.
  • Tau aggregates spread in a prion-like manner, contributing to cognitive decline.
  • Molecular mechanisms of tau aggregation and propagation are not fully understood.

Purpose of the Study:

  • To investigate the role of lysosomes in tau pathology and cognitive resilience in Alzheimer's disease.
  • To explore the mechanisms of tau propagation and its link to cognitive vulnerability.

Main Methods:

  • Analysis of human autopsy brain tissue (prefrontal cortex) from Braak stage VI patients with varying cognitive scores (CDR).
  • Isolation of lysosomal fractions from brain tissue.
  • Characterization of tau pathology within lysosomes.

Main Results:

  • Cognitively resilient AD patients exhibit intact lysosomal integrity and reduced tau pathology.
  • Cognitively vulnerable AD patients show compromised lysosomes containing partially digested, seed-competent tau proteins.
  • These tau species are secreted via lysosomal exocytosis, facilitating pathology spread and cognitive decline.

Conclusions:

  • Lysosomal integrity is crucial for modulating tau pathology and cognitive outcomes in AD.
  • Dysfunctional lysosomes drive tau propagation and severe cognitive decline.
  • Targeting lysosomal exocytosis pathways presents a potential therapeutic strategy for AD.