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Alzheimer's disease (AD) and vascular dementia (VaD) are the most common causes of dementia, and borderlines are blurred in many cases. Aging remains the main risk factor to suffer dementia; however, epidemiological studies reveal that diabetes may also predispose to suffer AD. In order to further study this relationship, we have induced hypoinsulinemic diabetes to APPswe/PS1dE9 (APP/PS1) mice, a classical model of AD. APP/PS1 mice received streptozotocin (STZ) ip at 18 weeks of age, when AD pathology is not yet established in this animal model. Cognition was evaluated at 26 weeks of age in the Morris water maze and the new object discrimination tests. We observed that STZ-induced episodic and working memory impairment was significantly worsened in APP/PS1 mice. Postmortem assessment included brain atrophy, amyloid-beta and tau pathology, spontaneous bleeding, and increased central inflammation. Interestingly, in APP/PS1-STZ diabetic mice, we detected a shift in Aβ soluble/insoluble levels, towards more toxic soluble species. Phospho-tau levels were also increased in APP/PS1-STZ mice, accompanied by an exacerbated inflammatory process, both in the close proximity to senile plaque (SP) and in SP-free areas. The presence of hemorrhages was significantly higher in APP/PS1-STZ mice, and although pericytes and endothelium were only partially affected, it remains possible that blood-brain barrier alterations underlie observed pathological features. Our data support the implication of the diabetic process in AD and VaD, and it is feasible that improving metabolic control could delay observed central pathology.
Pubmed ID: 26156287
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An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsA contract research organization providing drug development and animal testing services. Under the name Covance Research Products Inc., based in Denver, Pennsylvania, the company also deals in the import, breeding and sale of laboratory animals. It breeds dogs, rabbits, guinea pigs, non-human primates, and pigs, and runs the largest non-human primate laboratory in Germany. (Wikipedia)
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