The contribution of activated astrocytes to Aβ production: Implications for Alzheimers disease pathogenesis

摘要

Backgroundβ-Amyloid (Aβ) plays a central role in Alzheimer's disease (AD) pathogenesis. Neurons are major sources of Aβ in the brain. However, astrocytes outnumber neurons by at least five-fold. Thus, even a small level of astrocytic Aβ production could make a significant contribution to Aβ burden in AD. Moreover, activated astrocytes may increase Aβ generation. β-Site APP cleaving enzyme 1 (BACE1) cleavage of amyloid precursor protein (APP) initiates Aβ production. Here, we explored whether pro-inflammatory cytokines or Aβ42 would increase astrocytic levels of BACE1, APP, and β-secretase processing, implying a feed-forward mechanism of astrocytic Aβ production.