Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Apolipoprotein E interferes with IAPP aggregation and protects pericytes from IAPP-Induced Toxicity

Gharibyan, Anna L. ; Islam, Tohidul ; Pettersson, Nina ; Golchin, Solmaz A. ; Lundgren, Johanna ; Johansson, Gabriella ; Genot, Mélany ; Schultz, Nina LU ; Wennström, Malin LU and Olofsson, Anders (2020) In Biomolecules 10(1).
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Apolipoprotein E, Cytotoxicity, IAPP amyloid, Pericytes, Thioflavin T
in
Biomolecules
volume
10
issue
1
article number
134
publisher
MDPI AG
external identifiers
  • pmid:31947546
  • scopus:85077999664
ISSN
2218-273X
DOI
10.3390/biom10010134
language
English
LU publication?
yes
id
dee5f86a-c426-48f8-8489-ad891167eaa8
date added to LUP
2021-01-11 13:54:13
date last changed
2025-06-27 16:54:26
@article{dee5f86a-c426-48f8-8489-ad891167eaa8,
  abstract     = {{<p>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.</p>}},
  author       = {{Gharibyan, Anna L. and Islam, Tohidul and Pettersson, Nina and Golchin, Solmaz A. and Lundgren, Johanna and Johansson, Gabriella and Genot, Mélany and Schultz, Nina and Wennström, Malin and Olofsson, Anders}},
  issn         = {{2218-273X}},
  keywords     = {{Apolipoprotein E; Cytotoxicity; IAPP amyloid; Pericytes; Thioflavin T}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{MDPI AG}},
  series       = {{Biomolecules}},
  title        = {{Apolipoprotein E interferes with IAPP aggregation and protects pericytes from IAPP-Induced Toxicity}},
  url          = {{http://dx.doi.org/10.3390/biom10010134}},
  doi          = {{10.3390/biom10010134}},
  volume       = {{10}},
  year         = {{2020}},
}