Alzheimer's disease: a cell biological perspective

An almost bewildering number of findings concerning Alzheimer's disease mask the significant recent progress in understanding the molecular basis of some inherited forms of this disease and the proteolytic processing of proteins related to the disease. Alzheimer's disease is an amyloidosis, a condition in which certain proteins or protein fragments precipitate in various tissues as amyloid, fibrillar aggregates with a beta-pleated sheet conformation. Alzheimer's is also characterized by neuritic lesions and cell death. Some rare forms of the disease are now known to arise from a mutation in an amyloidogenic protein. Another recent insight is the discovery of an endosomal-lysosomal processing pathway capable of generating protein fragments that can deposit extracellularly as amyloid fibrils. Key future directions for cellular-based research in Alzheimer's disease include the study of membrane trafficking and the passage of intracellular material to the extracellular milieu, molecular signaling among intracellular compartments, the interaction between organelles and the neuronal cytoskeleton, and the nature of cytoskeletal reorganization after neuronal injury.