This project aims to study the pathological role of Extracellular vesicles (EVs) in human brain and the correlation between EVs secretion with whole brain proteome. EVs are extracted from human brain tissue of Alzheimer dementia (AD) patients, VaD patients and age matched healthy controls using PROSPR method. Alzheimer patients includes stage3 (AD3), stage4 (AD4), stage5 (AD5) and stage6 (AD6). Whole brain proteome are performed simultaneously. Proteins associated with pre-symptomatic AD, AD progression and other pathological ways are analysed. The potential targets are further validated with MRM approach