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Amylin alters human brain pericyte viability and NG2 expression

Schultz, Nina LU ; Byman, Elin LU ; Fex, Malin LU and Wennström, Malin LU (2017) In Journal of Cerebral Blood Flow and Metabolism 37(4). p.1470-1482
Abstract

Amylin, a pancreatic β-cell-derived peptide hormone, forms inclusions in brain microvessels of patients with dementia who have been diagnosed with type 2 diabetes and Alzheimer's disease. The cellular localization of these inclusions and the consequences thereof are not yet known. Using immunohistochemical staining of hippocampus and parahippocampal cortex from patients with Alzheimer's disease and non-demented controls, we show that amylin cell inclusions are found in pericytes. The number of amylin cell inclusions did not differ between patients with Alzheimer's disease and controls, but amylin-containing pericytes displayed nuclear changes associated with cell death and reduced expression of the pericyte marker neuron-glial antigen... (More)

Amylin, a pancreatic β-cell-derived peptide hormone, forms inclusions in brain microvessels of patients with dementia who have been diagnosed with type 2 diabetes and Alzheimer's disease. The cellular localization of these inclusions and the consequences thereof are not yet known. Using immunohistochemical staining of hippocampus and parahippocampal cortex from patients with Alzheimer's disease and non-demented controls, we show that amylin cell inclusions are found in pericytes. The number of amylin cell inclusions did not differ between patients with Alzheimer's disease and controls, but amylin-containing pericytes displayed nuclear changes associated with cell death and reduced expression of the pericyte marker neuron-glial antigen 2. The impact of amylin on pericyte viability was further demonstrated in in vitro studies, which showed that pericyte death increased in presence of fibril- and oligomer amylin. Furthermore, oligomer amylin increased caspase 3/7 activity, reduced lysate neuron-glial antigen 2 levels and impaired autophagy. Our findings contribute to increased understanding of how aggregated amylin affects brain vasculature and highlight amylin as a potential factor involved in microvascular pathology in dementia progression.

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organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Cerebral Blood Flow and Metabolism
volume
37
issue
4
pages
1470 - 1482
publisher
Nature Publishing Group
external identifiers
  • scopus:85026324171
  • wos:000400234000025
ISSN
1559-7016
DOI
10.1177/0271678X16657093
language
English
LU publication?
yes
id
ed8cbdce-6cbe-4442-843a-b3d3b2b64c0a
date added to LUP
2017-01-12 13:25:09
date last changed
2018-01-07 11:44:31
@article{ed8cbdce-6cbe-4442-843a-b3d3b2b64c0a,
  abstract     = {<p>Amylin, a pancreatic β-cell-derived peptide hormone, forms inclusions in brain microvessels of patients with dementia who have been diagnosed with type 2 diabetes and Alzheimer's disease. The cellular localization of these inclusions and the consequences thereof are not yet known. Using immunohistochemical staining of hippocampus and parahippocampal cortex from patients with Alzheimer's disease and non-demented controls, we show that amylin cell inclusions are found in pericytes. The number of amylin cell inclusions did not differ between patients with Alzheimer's disease and controls, but amylin-containing pericytes displayed nuclear changes associated with cell death and reduced expression of the pericyte marker neuron-glial antigen 2. The impact of amylin on pericyte viability was further demonstrated in in vitro studies, which showed that pericyte death increased in presence of fibril- and oligomer amylin. Furthermore, oligomer amylin increased caspase 3/7 activity, reduced lysate neuron-glial antigen 2 levels and impaired autophagy. Our findings contribute to increased understanding of how aggregated amylin affects brain vasculature and highlight amylin as a potential factor involved in microvascular pathology in dementia progression.</p>},
  author       = {Schultz, Nina and Byman, Elin and Fex, Malin and Wennström, Malin},
  issn         = {1559-7016},
  language     = {eng},
  number       = {4},
  pages        = {1470--1482},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Cerebral Blood Flow and Metabolism},
  title        = {Amylin alters human brain pericyte viability and NG2 expression},
  url          = {http://dx.doi.org/10.1177/0271678X16657093},
  volume       = {37},
  year         = {2017},
}