Combination therapy prevents amyloid-dependent and -independent structural changes.

ABSTRACT: Neuropathological features of Alzheimer's disease (AD) are recapitulated in transgenic mice expressing familial AD-causing mutations, but ectopic transgene overexpression makes it difficult to relate these abnormalities to disease pathogenesis. Alternatively, the APP/PS-1 double knock-in (DKI) mouse produces mutant amyloid precursor protein (APP) and presenilin-1 (PS-1) with normal levels and regulatory controls. Here, we investigated effects of amyloid on brain structure and neuroplasticity by vaccinating DKI mice with amyloid-β starting at 8 months of age. At 14 months, vaccination blocked cerebral amyloid deposition and its attendant microglial activation. Neuropil abnormalities were pronounced only within plaques, and included circumscribed loss and dysmorphology of axons, dendrites, t

SUBMITTER: Malthankar-Phatak G 

PROVIDER: S-EPMC3094748 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature