Human but not rat amylin shares neurotoxic properties with Aβ42 in long-term hippocampal and cortical cultures

Type 2 diabetes mellitus (DM) and Alzheimer's disease (AD) share epidemiological and biochemical features. Both are characterized by insoluble protein aggregates with a fibrillar conformation - amylin in Type 2 DM pancreatic islets, and A beta in AD brain. To determine whether amylin shares neurotoxic properties with A beta, we incubated hippocampal and cortical neurons with A beta 42 and human amylin. Different from non-amyloidogenic rat amylin, both caused a dose-, time- and cell type-specific neurotoxicity supporting the notion of a similar toxic mechanism. Depending on the cell type, this finding is also supported by co-incubation of human amylin and A beta. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.