Decreased Clearance of CNS β-Amyloid in Alzheimer’s Disease アルツハイマー病では中枢神経系のβアミロイドのクリアランスが低下している

Alzheimer’s disease is hypothesized to be caused by an imbalance between β-amyloid (Aβ) production and clearance leading 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. 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 to 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. アルツハイマー病（AD）アミロイド仮説では、ADはβアミロイド（Aβ）の産生と分解のバランスが崩れて起こるとされている。今回、中枢神経系（CNS）のAβ（Aβ42とAβ40）の産生と分解を測定する方法を開発し、対照と比較検討した結果、ADではAβの分解が低下していることが明らかになった。