Compilation of all known protein changes in the human Alzheimer's disease brain

Abstract

Proteomic studies of human Alzheimers disease brain tissue have exceptional potential to identify protein changes that drive disease and to identify new drug targets. Here, we detail a combined analysis of 38 published Alzheimers disease proteomic studies, generating a comprehensive map of protein changes in human brain tissue across thirteen brain regions, three disease stages (preclinical Alzheimers disease, mild cognitive impairment, advanced Alzheimers disease), and proteins enriched in amyloid plaques, neurofibrillary tangles, and cerebral amyloid angiopathy. Our dataset is compiled into a user-friendly, searchable database called NeuroPro. Our combined analysis included 18,119 reported protein differences in human Alzheimers disease brain tissue, which mapped to 5,311 total altered proteins. Proteomic studies were remarkably consistent. 848 proteins were consistently altered in [≥]5 studies, many of which are understudied in the Alzheimers field. Comparison of protein changes in early-stage and advanced Alzheimers disease revealed significant synapse, vesicle, and lysosomal changes early in disease, but widespread mitochondrial changes only in advanced Alzheimers disease. Comparison of vulnerable and resistant brain regions suggested that protein changes in resistant regions in advanced Alzheimers disease are similar to those in vulnerable regions in early-stage Alzheimers disease, indicating a temporal progression of protein dysfunction during Alzheimers disease advancement. We conclude that NeuroPro is a powerful new resource that provides new insights into human Alzheimers disease brain protein changes and highlights novel proteins of particular interest that may mechanistically drive Alzheimers disease.