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

Lim, Yun-An; Ittner, Lars M.; Lim, Yun Li; Götz, Jürgen

doi:10.1016/j.febslet.2008.05.006

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Volume 582, Issue 15 , Pages 2188-2194, 25 June 2008

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

Edited by Jesus Avila

Alzheimer’s and Parkinson’s Disease Laboratory, Brain and Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia

Received 3 February 2008; received in revised form 22 April 2008; accepted 5 May 2008. published online 15 May 2008.

Abstract

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 Aβ in AD brain. To determine whether amylin shares neurotoxic properties with Aβ, we incubated hippocampal and cortical neurons with Aβ42 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 Aβ.

Keywords: Aβ42 amyloid, Alzheimer’s disease, Amylin, Cell-type specificity, Conformational disease, IAPP, Neurotoxicity, Type 2 diabetes mellitus