Journal
JOURNAL OF PATHOLOGY
Volume 254, Issue 3, Pages 244-253Publisher
WILEY
DOI: 10.1002/path.5674
Keywords
Alzheimer' s disease; diabetes; IAPP; islet amyloid; MAPT; tau
Funding
- Diabetes Canada
- Canadian Institutes of Health Research (CIHR) [MOP-115056]
- Alzheimer's Society Canada
- Weston Brain Institute
- National Institute for Translational Neuroscience (INNT/Brazil)
- Brazilian funding agency Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Brazilian funding agency Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- Alzheimer Society of Ontario
Ask authors/readers for more resources
The combined effects of human tau and human IAPP in transgenic mice led to increased hyperglycaemia, insulin resistance, and glucose intolerance, reduced beta cell area and insulin content, increased amyloid deposition, and impaired insulin processing. This suggests a potential mechanism connecting Alzheimer's disease and type 2 diabetes through a coordinated impairment of beta cell function and glucose homeostasis by tau and IAPP amyloid.
Amyloid plaques and neurofibrillary tangles composed of hyperphosphorylated tau are important contributors to Alzheimer's disease (AD). Tau also impacts pancreatic beta cell function and glucose homeostasis. Amyloid deposits composed of islet amyloid polypeptide (IAPP) are a pathological feature of type 2 diabetes (T2D). The current study investigates the role of human tau (hTau) in combination with human IAPP (hIAPP) as a potential mechanism connecting AD and T2D. Transgenic mice expressing hTau and hIAPP in the absence of murine tau were generated to determine the impact of these pathological factors on glucose metabolism. Co-expression of hIAPP and hTau resulted in mice with increased hyperglycaemia, insulin resistance, and glucose intolerance. The hTau-hIAPP mice also exhibited reduced beta cell area, increased amyloid deposition, impaired insulin processing, and reduced insulin content in islets. Tau phosphorylation also increased after stimulation with high glucose. In addition, brain insulin content and signalling were reduced, and tau phosphorylation was increased in these animals. These data support a link between tau and IAPP amyloid, which seems to act co-ordinately to impair beta cell function and glucose homeostasis, and suggest that the combined pathological actions of these proteins may be a potential mechanism connecting AD and T2D. (c) 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available