The inflammation-induced pathological chaperones ACT and apo-E are necessary catalysts of Alzheimer amyloid formation

Biochemical, genetic, and epidemiological evidence indicates that inflammation is an essential part of the pathogenesis of Alzheimer’s disease. Over the last decade, we and others have focused on the mechanism by which specific inflammatory molecules contribute to the Alzheimer pathogenic pathway. In particular, we have learned that several acute phase/inflammatory molecules, specifically α1-antichymotrypsin (ACT) and apolipoprotein E (apoE) that are overproduced in the AD brain can promote the formation of, and are associated with, the neurotoxic amyloid deposits that are a key pathological hallmark of the disease. Because both of these proteins bind to the Aβ peptide and catalyze its polymerization into amyloid filaments, they have been termed “pathological chaperones”.