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APOE in the normal brain.

Sarah A Flowers1, G William Rebeck1

  • 1Department of Neuroscience, Georgetown University, 3970 Reservoir Rd, NW, Washington, DC 20007, United States of America.

Neurobiology of Disease
|January 9, 2020
PubMed
Summary

The APOE4 protein influences normal brain function and Alzheimer's disease (AD) risk. Understanding APOE genotype effects on brain structure and behavior may reveal new strategies for AD prevention.

Keywords:
APOEApolipoproteinFunctional MRIGlycosylationInflammationLipoproteinMouse model

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Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • The apolipoprotein E (APOE) genotype is a significant risk factor for Alzheimer's disease (AD).
  • APOE's role in AD pathogenesis is studied, but its impact on normal brain function is less understood.
  • APOE genotype influences neuropathological markers like amyloid plaques and neurofibrillary tangles.

Purpose of the Study:

  • To investigate the effects of APOE genotype on normal brain function.
  • To explore how APOE's central nervous system (CNS) properties differ from plasma properties.
  • To identify potential therapeutic targets for preventing AD by understanding APOE's role in aging brains.

Main Methods:

  • Review of post-translational modifications of APOE isoforms (glycosylation, lipidation, multimer formation).
  • Analysis of structural and functional studies in young human brains.
  • Examination of control APOE knock-in mouse models.

Main Results:

  • APOE genotype significantly impacts microscopic neuron structure, gross brain structure, and behavior.
  • Effects are primarily observed in hippocampal regions.
  • Differences in APOE isoforms affect normal brain processes.

Conclusions:

  • APOE's influence extends beyond AD hallmarks, affecting normal brain function.
  • Studying APOE in healthy brains can identify biomarkers for APOE dysfunction.
  • Targeting normal APOE function may offer new avenues for AD prevention.