Affiliations: [a] Neuroscience Research, Jesse Brown VA Medical Center, Chicago, IL, USA | [b] Department of Pediatrics, University of Illinois Hospital & Health Science System-Children's Hospital, University of Illinois at Chicago, Chicago, IL, USA | [c] Department of Biopharmaceutical Sciences, Roosevelt University, Schaumburg, IL, USA
Correspondence:
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Correspondence to: Neelima B. Chauhan, Ph.D., Neuroscience Research (151), Jesse Brown VA Medical Center, 820 South Damen Avenue, Chicago, IL 60612, USA. Tel.: +1 312 569 7747; Fax: +1 312 569 8114; E-mail: [email protected].
Abstract: Alzheimer's disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD.
Keywords: Alzheimer's disease, amyloid-β, diabetes, glycogen synthase kinase-3β, learning and memory, pathological aging of the brain, senescence-accelerated mice, synaptophysin, tau
