Adenovirus 36 improves glycemic control and markers of Alzheimer's disease pathogenesis

V. Hegde, M. Vijayan, S. Kumar, Md Akheruzzaman, N. Sawant, N. V. Dhurandhar, P. H. Reddy

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. While the causes of AD are unclear, several risk factors have been identified, including impaired glycemic control, which significantly increases the risk of cognitive decline and AD. In vitro and in vivo studies show that human adenovirus 36 (Ad36) improves glycemic control by increasing cellular glucose uptake in cells, experimental animal models and in humans who are naturally exposed to the virus. This study, tested improvement in glycemic control by Ad36 and delay in onset of cognitive decline in APPswe transgenic mice (Tg2576 line), a model of genetic predisposition to impaired glycemic control and AD. Three-month old APPswe mice were divided into Ad36 infected (Ad36) or mock infected (control) groups and baseline glycemic control measured by glucose tolerance test (GTT) prior to infection. Changes in glycemic control were determined 10- and 24-week post infection. Serum insulin was also measured during GTT. Cognition was determined by Y-maze test, while motor coordination and skill acquisition by rotarod test. Glycemic control as determined by GTT showed less deterioration in Ad36 infected mice over time, accompanied by a significant attenuation of cognitive decline. Analysis of brain tissue lysate showed significantly reduced levels of amyloid beta 42 in Ad36 mice relative to control mice. Golgi-Cox staining analysis also revealed reduced dendritic spines and synaptic gene expression in control mice compared to Ad36 infected mice. This proof of concept study shows that in a mouse model of AD, Ad36 improves glycemic control and ameliorates cognitive decline.

Original languageEnglish
Article number165531
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1865
Issue number11
DOIs
StatePublished - Nov 1 2019

Keywords

  • APP transgenic mice
  • Ad36
  • Alzheimer's disease
  • Amyloid beta
  • Cognition decline
  • Glycemic control

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