Journal
ACS CHEMICAL NEUROSCIENCE
Volume 7, Issue 3, Pages 269-274Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.5b00325
Keywords
Amyloid beta peptides; Alzheimer's disease; insulin; diabetes mellitus type II; cross amyloid interaction; fibrillation
Funding
- Magnus Bergvall foundation
- Swedish Research Council
- Brain Foundation
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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 beta (A beta) peptide fibrils. Prior to fibrillating, A beta forms intermediate, prefibrillar oligomers, which are more cytotoxic than the mature A beta fibrils. Insulin can also form amyloid fibrils. In vivo studies have revealed that insulin promotes the production of A beta, and that soluble A beta competes with insulin for the insulin receptor. Here, we report that monomeric insulin interacted with soluble A beta and that both molecules reciprocally slowed down the aggregation kinetics of the other. Prefibrillar oligomers of A beta that eventually formed in the presence of insulin were less cytotoxic than A beta oligomers formed in the absence of insulin. Mature A beta fibrils induced fibrillation of soluble insulin, but insulin aggregates did not promote A beta fibrillation. Our study indicates that direct molecular interactions between insulin and A beta may contribute to the strong link between DM and AD.
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