Seed-induced Aβ deposition is modulated by microglia under environmental enrichment in a mouse model of Alzheimer's disease
Ziegler-Waldkirch S, d'Errico P, Sauer JF, Erny D, Savanthrapadian S, Loreth D, Katzmarski N, Blank T, Bartos M, Prinz M, Meyer-Luehmann M.
Alzheimer's disease (AD) is characterized by severe neuronal loss as well as the accumulation of amyloid-β (Aβ), which ultimately leads to plaque formation. Here, we find that Aβ seeding, representing early stages of plaque formation, leads to a dramatic decrease in proliferation and neurogenesis in two APP transgenic mouse models. We further demonstrate that neuronal cell death occurs primarily in the vicinity of induced Aβ deposits culminating in electrophysiological abnormalities. Notably, environmental enrichment and voluntary exercise not only revives adult neurogenesis and reverses memory deficits but, most importantly, prevents Aβ seeding by activated, phagocytic microglia cells.
