Methodology for discovery of Alzheimer's disease blood-based biomarkers

Alzheimer's disease (AD) is a degenerative brain disorder. The disease also affects peripheral tissue such as peripheral blood mononuclear cells (PBMCs). Delineating biochemical alterations in AD blood constituents may possibly allow the identification of accessible footprints that reflect degenerative processes within the central nervous system. Here, we describe an integrated methodology for the generation of a blood-based molecular bio-repository, including the collection of clinical and demographic data for downstream stringent sample selection and stratification for the study of molecular signatures in AD. We report the simultaneous extraction of high quality and yield of DNA, RNA, and protein from PBMCs of individuals with sporadic AD, mild cognitive impairment, and normal elderly controls. We describe experimental designs and present examples for the discovery of underlying etiopathogenetic networks in sporadic AD. We suggest that PBMC-associated biomarkers may provide insights into the pathogenesis of AD and be used to monitor disease diagnosis and progression.