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

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2019-11, Vol.1865 (11), p.165531-165531, Article 165531
• Main Authors: Hegde, V., Vijayan, M., Kumar, S., Akheruzzaman, Md, Sawant, N., Dhurandhar, N.V., Reddy, P.H.
• Format: Article
• Language: English
• Subjects: Ad36; Adenoviridae - physiology; Adenoviridae Infections - blood; Adenoviridae Infections - complications; Adenoviridae Infections - pathology; Alzheimer Disease - blood; Alzheimer Disease - complications; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta; Amyloid beta-Peptides - analysis; Animals; APP transgenic mice; Blood Glucose - analysis; Cognition decline; Cognitive Dysfunction - blood; Cognitive Dysfunction - complications; Cognitive Dysfunction - pathology; Dendritic Spines - pathology; Disease Models, Animal; Glucose Tolerance Test; Glycemic control; Humans; Mice, Transgenic; Protective Factors
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2019.08.007

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. •Aging is a risk factor for glucose intolerance, development of T2D and AD.•Human adenovirus 36 (Ad36) improves glycemic control in vitro and in vivo.•In APP transgenic mice of AD, Ad36 infection improves glycemic control over time.•Ad36 infection prevents cognitive decline and reduces soluble amyloid beta (Aβ).•This underscores the association of peripheral glycemic control and AD pathology.