Very little studies have explored the role played by the specialized choroid plexus epithelial cells and the ependymal cells that line the ventricles. In normal and pathological (AD) ageing, reports of alterations in the blood brain CSF barrier (BCSFB) integrity and membrane transporters, accompanied by deficiencies in CSF production and an enlarged ventricular volume have been documented. The molecular sequelae of events driving these age-related pathological changes remains elusive. Given the pivotal role of the ventricular system in normal brain physiology, in this study we proposed to explore their contributing role towards AD pathogenesis. To address this, we used our state-of-the-art proteomic platform, a liquid chromatography/mass spectrometry (LC-MS) approach coupled with Tandem Mass Tag labeling technology to conduct a detailed characterization and assessment of molecular changes in protein expression levels from isolated tissue from the walls of the ventricles in autopsy AD cases, and two groups of age-matched control cases (non-agenarian’s with no AD pathology, and those with no clinical AD diagnosis but significant amyloid pathology and Braak staging).