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

Abstract 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.