Experimental induction of type 2 diabetes in aging-accelerated mice triggered alzheimer-like pathology and memory deficits

Jogender Mehla, Balwantsinh C. Chauhan, Neelima B. Chauhan

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

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.

Original languageEnglish
Pages (from-to)145-162
Number of pages18
JournalJournal of Alzheimer's Disease
Volume39
Issue number1
DOIs
StatePublished - 2014

Keywords

  • Alzheimer's disease
  • amyloid-β
  • diabetes
  • glycogen synthase kinase-3β
  • learning and memory
  • pathological aging of the brain
  • senescence-accelerated mice
  • synaptophysin
  • tau

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