Alzheimer's disease and the amyloid-beta peptide.
Alzheimer's disease (AD) pathogenesis is widely believed to be driven by the production and deposition of the amyloid-beta peptide (Abeta). For many years, investigators have been puzzled by the weak to nonexistent correlation between the amount of neuritic plaque pathology in the human brain and the degree of clinical dementia. Recent advances in our understanding of the development of amyloid pathology have helped solve this mystery. Substantial evidence now indicates that the solubility of Abeta, and the quantity of Abeta in different pools, may be more closely related to disease state. The composition of these pools of Abeta reflects different populations of amyloid deposits and has definite correlates with the clinical status of the patient. Imaging technologies, including new amyloid imaging agents based on the chemical structure of histologic dyes, are now making it possible to track amyloid pathology along with disease progression in the living patient. Interestingly, these approaches indicate that the Abeta deposited in AD is different from that found in animal models. In general, deposited Abeta is more easily cleared from the brain in animal models and does not show the same physical and biochemical characteristics as the amyloid found in AD. This raises important issues regarding the development and testing of future therapeutic agents.
Murphy
M Paul
MP
Department of Molecular and Cellular Biochemistry and the Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA. mpmurp3@email.uky.edu
LeVine
Harry
H
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D011487:Protein Conformation
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments