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When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
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Basic Science and Pathogenesis.

Gerald Wai-Yeung Cheng1, Hexiao Ding1, Kai-Hei Tse2

  • 1Hong Kong Polytechnic University, Kowloon, Kowloon, Hong Kong.

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Summary

Atherosclerosis may drive sporadic Alzheimer's disease by impairing astrocyte autophagy, hindering cholesterol transport to oligodendrocytes and causing demyelination. This pathway impacts brain health and neurodegeneration.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Metabolic Disorders

Background:

  • Astrocytes maintain the blood-brain barrier and supply cholesterol for myelination.
  • Alzheimer's disease (AD) is linked to vascular damage and white matter loss.
  • Apolipoprotein E4 (ApoE4) correlates with demyelination, but most AD is sporadic, suggesting other pathways.

Purpose of the Study:

  • To investigate the hypothesis that atherosclerotic plaques inhibit endothelial and astrocytic autophagy.
  • To determine if this inhibition leads to impaired cholesterol transport and demyelination.
  • To explore a novel pathway for sporadic Alzheimer's disease progression.

Main Methods:

  • Comparison of 7-month-old C57BL/6 control mice with apolipoprotein E knockout (ApoeKO) mice.
  • Assessment of white matter integrity using T2-weighted and magnetic resonance spectroscopy.
  • Histochemical analysis of atherosclerotic plaques, autophagy markers (TRIM47), myelination, and cell types.

Main Results:

  • ApoeKO mice exhibited increased lipid deposition in grey matter vasculature, indicating atherosclerosis.
  • A reduction in the endothelial cell autophagy marker TRIM47 was observed in ApoeKO mice.
  • No significant changes in astrocyte numbers were detected.

Conclusions:

  • Atherosclerosis may impair endothelial autophagy, potentially affecting astrocytic functions.
  • Further research is needed to confirm the impact on myelination and sporadic AD mechanisms.
  • Understanding astrocytic autophagy could reveal new factors in neurodegenerative disorders.