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Beta Amyloid Protein Clearance and Microglial Activation

  • Sally A. Frautschy
  • Greg M. Cole
  • March D. Ard

Abstract

Progression of AD involves a slow accumulation of Aβ peptide deposited extracellularly in the neuropil and vasculature of the brain. Aβ peptides of MW from 4 to 5 kD (Aβ40, Aβ42 or Aβ43) are normally produced by many cells, but the mutations in early onset familial AD (fAD) cause increased production of the rapidly aggregating Aβ1–42 (Borchelt et al. (1997); Younkin (1995)). However, in approximately 95% of cases of AD, there is Aβ accumulation without genetically increased Aβ production. Thus, in the vast majority of AD cases, which arise out of interaction of aging with genetic risk factors, other aspects of Aβ metabolism appear to be important. For example, the increased risk, and earlier onset, of AD from the apolipoprotein (Apo) E4 allele, which is strongest between 65 and 80 years of age, is not associated with increased Aβ production, but rather with reduced Aβ clearance or enhanced amyloid formation. Other potential genetic risk factors for late-onset AD may also influence AD pathogenesis at levels beyond Aβ production, including alpha-2 macroglobulin (Liao et al. 1998), alpha-1 antichymotrypsin (Thome et al. (1995)), interleukin 1 (Nicoll et al. (2000)), and transforming growth factor beta (Luedecking et al. (2000)). Although factors regulating Aβ degradation and clearance have received little attention compared with factors regulating Aβ production associated with early-onset AD genes, there is now a large enough literature to consider the issues.

Keywords

Microglial Activation Amyloid Precursor Protein Amyloid Plaque Senile Plaque Scavenger Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Sally A. Frautschy
  • Greg M. Cole
  • March D. Ard

There are no affiliations available

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