AUTHOR=Blume Tanja , Filser Severin , Jaworska Anna , Blain Jean-Francois , Koenig Gerhard , Moschke Katrin , Lichtenthaler Stefan F. , Herms Jochen TITLE=BACE1 Inhibitor MK-8931 Alters Formation but Not Stability of Dendritic Spines JOURNAL=Frontiers in Aging Neuroscience VOLUME=10 YEAR=2018 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2018.00229 DOI=10.3389/fnagi.2018.00229 ISSN=1663-4365 ABSTRACT=
Beta-site amyloid-precursor-protein cleaving enzyme 1 (BACE1) is the rate limiting protease in the production of the amyloid-beta peptide (Aβ), which is considered to be the causative agent in the pathogenesis of Alzheimer’s Disease (AD). Therefore, the therapeutic potential of pharmacological BACE1 inhibitors is currently tested in clinical trials for AD treatment. To ensure a positive clinical outcome it is crucial to identify and evaluate adverse effects associated with BACE1 inhibition. Preclinical studies show that chronic blockade of BACE1 activity alters synaptic functions and leads to loss of dendritic spines. To assess the mechanism of synapse loss, dendritic spine dynamics of pyramidal layer V cells were monitored by