Article

Decreased Clearance of CNS -Amyloid in Alzheimer's Disease

Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Science (Impact Factor: 33.61). 12/2010; 330(6012):1774. DOI: 10.1126/science.1197623
Source: PubMed

ABSTRACT

Alzheimer’s disease is hypothesized to be caused by an imbalance between β-amyloid (Aβ) production and clearance that leads
to Aβ accumulation in the central nervous system (CNS). Aβ production and clearance are key targets in the development of
disease-modifying therapeutic agents for Alzheimer’s disease. However, there has not been direct evidence of altered Aβ production
or clearance in Alzheimer’s disease. By using metabolic labeling, we measured Aβ42 and Aβ40 production and clearance rates
in the CNS of participants with Alzheimer’s disease and cognitively normal controls. Clearance rates for both Aβ42 and Aβ40
were impaired in Alzheimer’s disease compared with controls. On average, there were no differences in Aβ40 or Aβ42 production
rates. Thus, the common late-onset form of Alzheimer’s disease is characterized by an overall impairment in Aβ clearance.

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