title: Experimental induction of type 2 diabetes in aging-accelerated mice triggered Alzheimer-like pathology and memory deficits.
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.
authors.affiliation: Neuroscience Research, Jesse Brown VA Medical Center, Chicago, IL, USA Department of Pediatrics, University of Illinois Hospital & Health Science System-Children's Hospital, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Jogender
authors.initials: J
authors.lastname: Mehla
authors.affiliation: Department of Biopharmaceutical Sciences, Roosevelt University, Schaumburg, IL, USA.
authors.forename: Balwantsinh C
authors.initials: BC
authors.lastname: Chauhan
authors.affiliation: Neuroscience Research, Jesse Brown VA Medical Center, Chicago, IL, USA Department of Pediatrics, University of Illinois Hospital & Health Science System-Children's Hospital, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Neelima B
authors.initials: NB
authors.lastname: Chauhan
mesh_terms: D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism*; D004041:Dietary Fats; D004195:Disease Models, Animal; D008569:Memory Disorders / Q000209:etiology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016708:Synaptophysin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D016708:Synaptophysin; D016875:tau Proteins
keywords: Alzheimer's disease; amyloid-β; diabetes; glycogen synthase kinase-3β; learning and memory; pathological aging of the brain; senescence-accelerated mice; synaptophysin; tau