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Open AccessArticle

Apolipoprotein E Interferes with IAPP Aggregation and Protects Pericytes from IAPP-Induced Toxicity

Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, 21428 Malmö, Sweden
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 134;
Received: 4 November 2019 / Revised: 10 January 2020 / Accepted: 12 January 2020 / Published: 14 January 2020
Apolipoprotein E (ApoE) has become a primary focus of research after the discovery of its strong linkage to Alzheimer’s disease (AD), where the ApoE4 variant is the highest genetic risk factor for this disease. ApoE is commonly found in amyloid deposits of different origins, and its interaction with amyloid-β peptide (Aβ), the hallmark of AD, is well known. However, studies on the interaction of ApoEs with other amyloid-forming proteins are limited. Islet amyloid polypeptide (IAPP) is an amyloid-forming peptide linked to the development of type-2 diabetes and has also been shown to be involved in AD pathology and vascular dementia. Here we studied the impact of ApoE on IAPP aggregation and IAPP-induced toxicity on blood vessel pericytes. Using both in vitro and cell-based assays, we show that ApoE efficiently inhibits the amyloid formation of IAPP at highly substoichiometric ratios and that it interferes with both nucleation and elongation. We also show that ApoE protects the pericytes against IAPP-induced toxicity, however, the ApoE4 variant displays the weakest protective potential. Taken together, our results suggest that ApoE has a generic amyloid-interfering property and can be protective against amyloid-induced cytotoxicity, but there is a loss of function for the ApoE4 variant. View Full-Text
Keywords: apolipoprotein E; IAPP amyloid; Thioflavin T; pericytes; cytotoxicity apolipoprotein E; IAPP amyloid; Thioflavin T; pericytes; cytotoxicity
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Gharibyan, A.L.; Islam, T.; Pettersson, N.; Golchin, S.A.; Lundgren, J.; Johansson, G.; Genot, M.; Schultz, N.; Wennström, M.; Olofsson, A. Apolipoprotein E Interferes with IAPP Aggregation and Protects Pericytes from IAPP-Induced Toxicity. Biomolecules 2020, 10, 134.

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