Amyloid Accumulation Drives Proteome-wide Alterations in Mouse Models of Alzheimer's Disease-like Pathology.

ABSTRACT: Amyloid beta (A?) peptides impair multiple cellular pathways and play a causative role in Alzheimer's disease (AD) pathology, but how the brain proteome is remodeled by this process is unknown. To identify protein networks associated with AD-like pathology, we performed global quantitative proteomic analysis in three mouse models at young and old ages. Our analysis revealed a robust increase in Apolipoprotein E (ApoE) levels in nearly all brain regions with increased A? levels. Taken together with prior findings on ApoE driving A? accumulation, this analysis points to a pathological dysregulation of the ApoE-A? axis. We also found dysregulation of protein networks involved in excitatory synaptic transmission. Analysis of the AMPA receptor (AMPAR) complex revealed specific loss of TARP?-2, a key AMPAR-trafficking protein. Expression of TARP?-2 in hAPP transgenic mice restored AMPA currents. This proteomic database represents a resource for the identification of protein alterations responsible for AD.

SUBMITTER: Savas JN 

PROVIDER: S-EPMC5726791 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature