title: Reciprocal Molecular Interactions between the Aβ Peptide Linked to Alzheimer's Disease and Insulin Linked to Diabetes Mellitus Type II.
abstract: Clinical studies indicate diabetes mellitus type II (DM) doubles the risk that a patient will also develop Alzheimer's disease (AD). DM is caused by insulin resistance and a relative lack of active insulin. AD is characterized by the deposition of amyloid β (Aβ) peptide fibrils. Prior to fibrillating, Aβ forms intermediate, prefibrillar oligomers, which are more cytotoxic than the mature Aβ fibrils. Insulin can also form amyloid fibrils. In vivo studies have revealed that insulin promotes the production of Aβ, and that soluble Aβ competes with insulin for the insulin receptor. Here, we report that monomeric insulin interacted with soluble Aβ and that both molecules reciprocally slowed down the aggregation kinetics of the other. Prefibrillar oligomers of Aβ that eventually formed in the presence of insulin were less cytotoxic than Aβ oligomers formed in the absence of insulin. Mature Aβ fibrils induced fibrillation of soluble insulin, but insulin aggregates did not promote Aβ fibrillation. Our study indicates that direct molecular interactions between insulin and Aβ may contribute to the strong link between DM and AD.
authors.affiliation: Gorlaeus Laboratory, Leiden Institute of Chemistry, Leiden University , 2300RA Leiden, The Netherlands.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University , SE-10691 Stockholm, Sweden.
authors.forename: Sebastian K T S
authors.initials: SK
authors.lastname: Wärmländer
authors.affiliation: Department of Biochemistry and Biophysics, Stockholm University , SE-10691 Stockholm, Sweden.
authors.forename: Astrid
authors.initials: A
authors.lastname: Gräslund
authors.affiliation: Gorlaeus Laboratory, Leiden Institute of Chemistry, Leiden University , 2300RA Leiden, The Netherlands.
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Abrahams
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism*; D018625:Microscopy, Atomic Force
chemical_list: D016229:Amyloid beta-Peptides; D007328:Insulin
keywords: Alzheimer’s disease; Amyloid β peptides; cross amyloid interaction; diabetes mellitus type II; fibrillation; insulin