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

PLoS One. 2019 Jun 17;14(6):e0218561. doi: 10.1371/journal.pone.0218561. eCollection 2019.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Islet Amyloid Polypeptide / blood*
  • Islet Amyloid Polypeptide / cerebrospinal fluid*
  • Male
  • Middle Aged
  • Prognosis
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Islet Amyloid Polypeptide
  • tau Proteins

Grant support

This work was supported by Swedish Research Council 521-2013-3448, https://www.vr.se; Petrus and Augusta Hedlund foundation 2016-0493, http://www.hedlundsstiftelse.se; Swedish Dementia foundation 2017, http://www.demensforbundet.se/sv/stod-oss/demensfonden/; Åke Wiberg foundation M17-0025, http://ake-wiberg.se; Åhlén foundation mC23 h18, http://www.ahlenstiftelsen.se; Crafoord foundation 20180776, https://www.crafoord.se; Greta and Johan Kocks foundations 2018, http://www.kockskastiftelsen.se; Alzheimer foundation AF-640421, https://www.alzheimerfonden.se; Olle Engkvist 194-0643 http://engkviststiftelserna.se to MW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.