Quantitative proteomics reveals distinct composition of amyloid plaques in Alzheimer's disease

Introduction: We investigated the proteomic profiles of amyloid plaques (APs) from Alzheimer's disease (AD) and age-matched non-AD brains and APP/PS1 transgenic model mice. Methods: APs and adjacent control regions were collected from fresh-frozen brain sections using laser capture dissection. Proteins were quantitated using tag-labeling coupled high-throughput mass spectra. Results: Over 4000 proteins were accurately quantified, and more than 40 were identified as highly enriched in both AD and non-AD APs, including apoE, midkine, VGFR1, and complement C4. Intriguingly, proteins including synaptic structural proteins and complement C1r, C5, and C9 were found to be upregulated in AD APs but not non-AD APs. Moreover, the proteomic pattern of AD APs was distinct from APP/PS1 APs and exhibited correlation with aging hippocampus. Discussion: Our results provide new insight into AP composition. We demonstrate unexpected differences between AD, non-AD, and APP/PS1 mouse APs, which may relate to different pathological processes. (C) 2018 Published by Elsevier Inc. on behalf of the Alzheimer's Association.