Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APP _Sw,Ind ) mice

TLDR

Neurogenesis persists in the adult brain and is heightened in certain pathological conditions. The study demonstrates that Alzheimer’s disease–induced neurogenesis can be replicated in a transgenic mouse model. PDGF‑APP Sw,Ind mice show a ~2‑fold increase in BrdUrd‑labeled cells and immature neuronal markers in the dentate gyrus and subventricular zone at 3 months, before neuronal loss or amyloid deposition, indicating that Alzheimer’s disease itself drives enhanced neurogenesis—likely via subtle dysfunction such as impaired neurotransmission—and suggesting a compensatory response that could be therapeutically targeted.

Abstract

Neurogenesis continues in the adult brain and is increased in certain pathological states. We reported recently that neurogenesis is enhanced in hippocampus of patients with Alzheimer's disease (AD). We now report that the effect of AD on neurogenesis can be reproduced in a transgenic mouse model. PDGF-APP Sw,Ind mice, which express the Swedish and Indiana amyloid precursor protein mutations, show increased incorporation of BrdUrd and expression of immature neuronal markers in two neuroproliferative regions: the dentate gyrus and subventricular zone. These changes, consisting of ≈2-fold increases in the number of BrdUrd-labeled cells, were observed at age 3 months, when neuronal loss and amyloid deposition are not detected. Because enhanced neurogenesis occurs in both AD and an animal model of AD, it seems to be caused by the disease itself and not by confounding clinical factors. As neurogenesis is increased in PDGF-APP Sw,Ind mice in the absence of neuronal loss, it must be triggered by more subtle disease manifestations, such as impaired neurotransmission. Enhanced neurogenesis in AD and animal models of AD suggests that neurogenesis may be a compensatory response and that measures to enhance neurogenesis further could have therapeutic potential.