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Detection of Neuritic Plaques in Alzheimer's Disease Mouse Model
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Detection of Neuritic Plaques in Alzheimer's Disease Mouse Model

Published on: July 26, 2011

alpha2-macroglobulin in late-onset Alzheimer's disease

D M Kovacs1

  • 1Genetics and Aging Unit, Massachusetts General Hospital, Harvard Medical School, Building 149,13th Street, Charlestown, MA 02129, USA. kovacs@helix.mgh.harvard.edu

Experimental Gerontology
|August 26, 2000
PubMed

Insights

Alpha2-macroglobulin (alpha(2)M), a brain protein, is linked to Alzheimer's disease (AD) pathogenesis. Genetic evidence shows A2M gene variations increase amyloid plaque accumulation in AD brains.

Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Alpha2-macroglobulin (alpha(2)M) is a plasma protein also produced in the brain.
  • In the brain, alpha(2)M binds ligands and is internalized by neurons and astrocytes.
  • Alpha(2)M is found in amyloid plaques in Alzheimer's disease (AD) brains.

Purpose of the Study:

  • To investigate the role of alpha2-macroglobulin (alpha(2)M) in Alzheimer's disease (AD) pathogenesis.
  • To explore the association between A2M gene polymorphisms and amyloid plaque accumulation in AD.

Main Methods:

  • Localization of alpha(2)M in AD brains.
  • Assessment of alpha(2)M binding to soluble beta-amyloid.
  • Analysis of genetic evidence linking A2M gene polymorphisms to AD.

Main Results:

  • Alpha(2)M binds soluble beta-amyloid and mediates its degradation.
  • An excess of alpha(2)M may exert neurotoxic effects.
  • DNA polymorphisms in the A2M gene are associated with increased amyloid plaque accumulation in AD brains.

Conclusions:

  • Alpha2-macroglobulin (A2M) is recognized as a late-onset Alzheimer's disease gene.
  • A2M plays a significant role in the etiopathology of Alzheimer's disease.

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