Biomarkers of Alzheimer disease in plasma

Plasma and serum biochemical markers proposed for Alzheimer disease (AD) are based on pathophysiologic processes such as amyloid plaque formation [amyloid beta-protein (A beta), A beta autoantibodies, platelet amyloid precursor protein (APP) isoforms], inflammation (cytokines), oxidative stress (vitamin E, isoprostanes), lipid metabolism (apolipoprotein E, 24S-hydroxycholesterol), and vascular disease [homocysteine, lipoprotein (a)]. Most proteins or metabolites evaluated in plasma or serum thus far are, at best, biological correlates of AD: levels are statistically different in AD versus controls in some cohorts, but they lack sensitivity or specificity for diagnosis or for tracking response to therapy. Approaches combining panels of existing biomarkers or surveying the range of proteins in plasma (proteomics) show promise for discovering biomarker profiles that are characteristic of AD, yet distinct from nondemented patients or patients with other forms of dementia.