Human but not rat amylin shares neurotoxic properties with Abeta42 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 Abeta in AD brain. To determine whether amylin shares neurotoxic properties with Abeta, we incubated hippocampal and cortical neurons with Abeta42 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 Abeta.
Lim
Yun-An
YA
Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia.
Ittner
Lars M
LM
Lim
Yun Li
YL
Götz
Jürgen
J
D000595:Amino Acid Sequence; D000682:Amyloid / Q000633:toxicity*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D006801:Humans; D058228:Islet Amyloid Polypeptide; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats
D000682:Amyloid; D016229:Amyloid beta-Peptides; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)