Role of biochemical Alzheimer's disease biomarkers as end points in clinical trials.

Amyloid-beta (Abeta) peptides, and total and phosphorylated tau are potential biomarkers for use in the development of treatments for Alzheimer's disease. Abeta(1-41) forms extracellular amyloid plaques, while tau and phospho-tau form intracellular neurofibrillary tangles in the brains of Alzheimer's disease patients. Plasma and cerebrospinal fluid concentrations of Abeta decreased following the clinical administration of gamma-secretase inhibitors and increased following the clinical administration of an anti-Abeta antibody. Therapies targeting Abeta decreased tau and phospho-tau concentrations in the cerebrospinal fluid. These biochemical biomarkers appear to be useful to establish therapeutic dosing for Phase III trials. Pivotal registration trials that rely on clinical measures as primary end points can utilize biochemical biomarkers as secondary outcomes indirectly measuring Alzheimer's disease pathology.