Poster Presentation 23rd Annual Lorne Proteomics Symposium 2018

Proteomics analysis of specific brain regions from Alzheimer's disease model mice at the early stage of disease pathology (#138)

Liting Deng 1 , Mehdi Mirzaei 1 , Vivek Gupta 1 , Yunqi Wu 1 , Stuart Graham 1 , Paul Haynes 1
  1. Macquarie University, North Sydney, NSW, Australia

Alzheimer's disease is considered a progressive multifarious neurodegenerative disorder and known as a foremost cause of dementia in late adult life. The pathogenesis of Alzheimer’s disease (AD), especially the early events of AD pathology, remains undetermined, chiefly due to the complexity of AD and failure in diagnoses of the disease in the early stages. Proteomics analysis has provided comprehensive insights to investigate the complex cellular activity in the brain both in human and animal studies, however, only limited studies were performed on the brain of the early AD individuals or young transgenic AD animal models. Here, we report the most comprehensive proteomic analysis of the most vulnerable brain area (hippocampus, frontal and parietal cortex) and less susceptible brain region (cerebellum) of 2.5-month-old of APP/PS1 transgenic mouse model of the AD and age-matched control animals. Multiplexed Tandem Mass Tag based proteomics was carried out on different brain region of APP/PS1 and wild-type animals.  Further, comprehensive functional pathway and protein network interaction analysis performed using Ingenuity, STRING, and Panther analysis tools. Selected differentially modulated proteins were validated using western blotting. Approximately 4500 proteins were identified and quantified (1% FDR) from each brain region.  Our data revealed that 471, 352, 226 and 33 proteins were up-regulated and 374, 466, 251 and 31 proteins were down-regulated in the hippocampus, frontal cortex, parietal cortex, and cerebellum respectively. In agreement with previous findings in the literature, the cerebellum is the least affected brain region in AD, despite beta-amyloid protein being identified as consistently up-regulated in all 4 different brain regions in APP mice model as compared to the control animals. Further, pathway enrichment analysis of differentially expressed proteins revealed that the most enriched biological pathways in the affected areas were associated with endocannabinoid signalling, glutamatergic synapse, GABAergic synapse, calcium signalling and mitochondrial dysfunction.