Amyloid-β and islet amyloid pathologies link Alzheimer's disease and type 2 diabetes in a transgenic model

Nadeeja Wijesekara*, Rosemary Ahrens, Miheer Sabale, Ling Wu, Kathy Ha, Giuseppe Verdile, Paul E. Fraser

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Alzheimer's disease (AD) and type 2 diabetes (T2D) present a significant risk to each other. AD and T2D are characterized by deposition of cerebral amyloid-β (A β) and pancreatic human islet amyloid polypeptide (hIAPP), respectively. We investigated the role of amyloidogenic proteins in the interplay between these diseases. A novel double transgenic mouse model combining T2D and AD was generated and characterized. AD-related amyloid transgenic mice coexpressing hIAPP displayed peripheral insulin resistance, hyperglycemia, and glucose intolerance. Aβ and IAPP amyloidco-deposition increased tau phosphorylation, and a reduction in pancreatic beta-cell mass was detected inislets. Increased brain A beta deposition and tau phosphorylation and reduced insulin levels and signaling were accompanied by extensive synaptic loss and decreased neuronal counts. Aβ immunization rescued the peripheral insulin resistance and hyperglycemia, suggesting a role for Aβ in T2D pathogenesis for individuals predisposed to AD. These findings demonstrate that Ab and IAPP are key factors in the overlapping pathologies of AD and T2D.

Original languageEnglish
Pages (from-to)5409-5418
Number of pages10
JournalFASEB Journal
Volume31
Issue number12
DOIs
Publication statusPublished - Dec 2017
Externally publishedYes

Keywords

  • insulin resistance
  • beta cells
  • tau
  • neurodegeneration
  • hyperglycemia

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