Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease

Background: We evaluated the amounts of amyloid beta (A beta)) peptides in the central nervous system (CNS) and in reservoirs outside the CNS and their potential impact on A beta plasma levels and Alzheimer's disease (AD) pathology. Methods: Amyloid beta levels were measured in (1) the plasma of AD and nondemented (ND) controls in a longitudinal study, (2) the plasma of a cohort of AD patients receiving a cholinesterase inhibitor, and (3) the skeletal muscle, liver, aorta, platelets, leptomeningeal arteries, and in gray and white matter of AD and ND control subjects. Results: Plasma A beta levels fluctuated over time and among individuals, suggesting continuous contributions from brain and peripheral tissues and associations with reactive circulating proteins. Arteries with atherosclerosis had larger amounts of A beta 40 than disease-free vessels. Inactivated platelets contained more A beta peptides than activated ones. Substantially more A beta was present in liver samples from ND patients. Overall, AD brain and skeletal muscle contained increased levels of A beta. Conclusions: Efforts to use plasma levels of A beta peptides as AD biomarkers or disease-staging scales have failed. Peripheral tissues might contribute to both the circulating amyloid pool and AD pathology within the brain and its vasculature. The wide spread of plasma A beta values is also due in part to the ability of A beta to bind to a variety of plasma and membrane proteins. Sources outside the CNS must be accounted for because pharmacologic interventions to reduce cerebral amyloid are assessed by monitoring A beta plasma levels. Furthermore, the long-range impact of A beta immunotherapy on peripheral A beta sources should also be considered. (C) 2009 The Alzheimer's Association. All rights reserved.