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 (Hemachandra) Reddy

    Research output: Contribution to journalArticle

    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 (US)
    Article number165531
    JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
    Volume1865
    Issue number11
    DOIs
    StatePublished - Nov 1 2019

    Fingerprint

    Adenoviridae
    Alzheimer Disease
    Glucose Tolerance Test
    Rotarod Performance Test
    Human Adenoviruses
    Dendritic Spines
    Motor Skills
    Genetic Predisposition to Disease
    Infection
    Amyloid
    Neurodegenerative Diseases
    Cognition
    Transgenic Mice
    Animal Models
    Insulin
    Staining and Labeling
    Viruses
    Gene Expression
    Glucose
    Control Groups

    Keywords

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

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology

    Cite this

    Hegde, V., Vijayan, M., Kumar, S., Akheruzzaman, M., Sawant, N., Dhurandhar, N. V., & Reddy, P. H. (2019). Adenovirus 36 improves glycemic control and markers of Alzheimer's disease pathogenesis. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1865(11), [165531]. https://doi.org/10.1016/j.bbadis.2019.08.007

    Adenovirus 36 improves glycemic control and markers of Alzheimer's disease pathogenesis. / Hegde, V.; Vijayan, M.; Kumar, S.; Akheruzzaman, Md; Sawant, N.; Dhurandhar, N. V.; Reddy, P (Hemachandra).

    In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1865, No. 11, 165531, 01.11.2019.

    Research output: Contribution to journalArticle

    Hegde, V, Vijayan, M, Kumar, S, Akheruzzaman, M, Sawant, N, Dhurandhar, NV & Reddy, PH 2019, 'Adenovirus 36 improves glycemic control and markers of Alzheimer's disease pathogenesis', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1865, no. 11, 165531. https://doi.org/10.1016/j.bbadis.2019.08.007
    Hegde, V. ; Vijayan, M. ; Kumar, S. ; Akheruzzaman, Md ; Sawant, N. ; Dhurandhar, N. V. ; Reddy, P (Hemachandra). / Adenovirus 36 improves glycemic control and markers of Alzheimer's disease pathogenesis. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2019 ; Vol. 1865, No. 11.
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