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Levels of islet amyloid polypeptide in cerebrospinal fluid and plasma from patients with Alzheimer’s disease

Schultz, Nina LU ; Janelidze, Shorena LU ; Byman, Elin LU ; Minthon, Lennart LU ; Nägga, Katarina LU ; Hansson, Oskar LU and Wennström, Malin LU (2019) In PLoS ONE 14(6).
Abstract

The biologically active pancreatic hormone peptide islet amyloid polypeptide (IAPP) regulates brain functions such as appetite and cognition. It also plays a role in clearance of amyloid beta (Aβ), a peptide implicated in the dementia disorder Alzheimer’s disease (AD). If IAPP becomes modified, it loses its biological activity and starts to aggregate. Such aggregations have been found in the AD brain and decreased plasma levels of the unmodified IAPP (uIAPP) have been shown in the same patients. In the current study, we analyze levels of uIAPP and total IAPP (unmodified and modified) in cerebrospinal fluid (CSF) to investigate its potential as a biomarker for AD. We found no differences in neither CSF nor plasma levels of uIAPP or total... (More)

The biologically active pancreatic hormone peptide islet amyloid polypeptide (IAPP) regulates brain functions such as appetite and cognition. It also plays a role in clearance of amyloid beta (Aβ), a peptide implicated in the dementia disorder Alzheimer’s disease (AD). If IAPP becomes modified, it loses its biological activity and starts to aggregate. Such aggregations have been found in the AD brain and decreased plasma levels of the unmodified IAPP (uIAPP) have been shown in the same patients. In the current study, we analyze levels of uIAPP and total IAPP (unmodified and modified) in cerebrospinal fluid (CSF) to investigate its potential as a biomarker for AD. We found no differences in neither CSF nor plasma levels of uIAPP or total IAPP in AD patients compared to cognitive healthy individuals (NC). The levels of uIAPP in CSF of NC were positively correlated with uIAPP in plasma, Q-albumin and albumin levels in CSF, but negatively correlated with CSF levels of t-tau and p-tau. These findings were not seen in AD patients. Levels of total CSF IAPP correlated positively with total Q-albumin and albumin levels in CSF in both AD and NC. In addition, total plasma IAPP correlated positively with CSF t-tau and p-tau in NC and negatively with CSF Aβ42 in AD patients. To conclude, our studies did not find evidence supporting the use of CSF IAPP as an AD biomarker. However, our findings, indicating a compromised translocation of uIAPP in and out of the brain in AD patients as well as the correlations between total plasma IAPP and AD biomarkers, encourage further research on the role for IAPP in AD.

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author
organization
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Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
14
issue
6
publisher
Public Library of Science
external identifiers
  • scopus:85067316370
ISSN
1932-6203
DOI
10.1371/journal.pone.0218561
language
English
LU publication?
yes
id
11310492-d3b1-4c36-9a09-8cad15472822
date added to LUP
2019-06-28 11:29:48
date last changed
2019-07-30 05:05:14
@article{11310492-d3b1-4c36-9a09-8cad15472822,
  abstract     = {<p>The biologically active pancreatic hormone peptide islet amyloid polypeptide (IAPP) regulates brain functions such as appetite and cognition. It also plays a role in clearance of amyloid beta (Aβ), a peptide implicated in the dementia disorder Alzheimer’s disease (AD). If IAPP becomes modified, it loses its biological activity and starts to aggregate. Such aggregations have been found in the AD brain and decreased plasma levels of the unmodified IAPP (uIAPP) have been shown in the same patients. In the current study, we analyze levels of uIAPP and total IAPP (unmodified and modified) in cerebrospinal fluid (CSF) to investigate its potential as a biomarker for AD. We found no differences in neither CSF nor plasma levels of uIAPP or total IAPP in AD patients compared to cognitive healthy individuals (NC). The levels of uIAPP in CSF of NC were positively correlated with uIAPP in plasma, Q-albumin and albumin levels in CSF, but negatively correlated with CSF levels of t-tau and p-tau. These findings were not seen in AD patients. Levels of total CSF IAPP correlated positively with total Q-albumin and albumin levels in CSF in both AD and NC. In addition, total plasma IAPP correlated positively with CSF t-tau and p-tau in NC and negatively with CSF Aβ<sub>42</sub> in AD patients. To conclude, our studies did not find evidence supporting the use of CSF IAPP as an AD biomarker. However, our findings, indicating a compromised translocation of uIAPP in and out of the brain in AD patients as well as the correlations between total plasma IAPP and AD biomarkers, encourage further research on the role for IAPP in AD.</p>},
  articleno    = {e0218561},
  author       = {Schultz, Nina and Janelidze, Shorena and Byman, Elin and Minthon, Lennart and Nägga, Katarina and Hansson, Oskar and Wennström, Malin},
  issn         = {1932-6203},
  language     = {eng},
  month        = {06},
  number       = {6},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Levels of islet amyloid polypeptide in cerebrospinal fluid and plasma from patients with Alzheimer’s disease},
  url          = {http://dx.doi.org/10.1371/journal.pone.0218561},
  volume       = {14},
  year         = {2019},
}