alpha 2-macroglobulin in late-onset Alzheimer's disease

alpha 2-macroglobulin (alpha(2)M) is an abundant plasma protein similar in structure and function to a group of proteins called alpha-macroglobulins. alpha(2)M is also produced in the brain where it binds multiple extracellul ar ligands and is internalized by neurons and astrocytes. In the brain of A lzheimer's disease (AD) patients, alpha(2)M has been localized to diffuse a myloid plaques. alpha(2)M also binds soluble beta-amyloid, of which it medi ates degradation. However, an excess of alpha(2)M can also have neurotoxic effects. Based on genetic evidence, is now recognized as one of the two con firmed late onset AD genes. As for the three early onset genes (the amyloid beta-protein precursor and the two presenilins) and for the other late ons et gene (ApoE), DNA polymorphisms in the A2M gene associated with AD result in significantly increased accumulation of amyloid plaques in AD brains. T hese data support an important role for A2M in AD etiopathology. (C) 2000 P ublished by Elsevier Science Inc.