Feng Xiong1, Wei Ge2, Chao Ma3. 1. State Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. 2. State Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. Electronic address: wei.ge@chem.ox.ac.uk. 3. Department of Human Anatomy, Histology and Embryology, Neuroscience Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. Electronic address: machao@ibms.cams.cn.
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.
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/PS1mouse APs, which may relate to different pathological processes.
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