Chronic γ-secretase inhibition reduces amyloid plaque-associated instability of pre- and postsynaptic structures.

ABSTRACT: The loss of synapses is a strong histological correlate of the cognitive decline in Alzheimer's disease (AD). Amyloid β-peptide (Aβ), a cleavage product of the amyloid precursor protein (APP), exerts detrimental effects on synapses, a process thought to be causally related to the cognitive deficits in AD. Here, we used in vivo two-photon microscopy to characterize the dynamics of axonal boutons and dendritic spines in APP/Presenilin 1 (APP(swe)/PS1(L166P))-green fluorescent protein (GFP) transgenic mice. Time-lapse imaging over 4 weeks revealed a pronounced, concerted instability of pre- and postsynaptic structures within the vicinity of amyloid plaques. Treatment with a novel sulfonamide-type γ-secretase inhibitor (GSI) attenuated the formation and growth of new plaques and, most importan

SUBMITTER: Liebscher S 

PROVIDER: S-EPMC4113951 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature