Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication. | ||||||||
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Alzheimer-like changes in rat models of spontaneous diabetes.Li ZG, Zhang W, Sima AA Department of Pathology, Wayne State University, School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA. OBJECTIVE: To examine whether changes characteristic of Alzheimer's disease occur in two rat models with spontaneous onset of type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: The frontal cortices of 8-month-diabetic rats were examined with respect to neuronal densities, neurite degeneration, expression, and/or immunolocalization of amyloid precursor protein (APP), beta-secretase, beta-amyloid, COOH-terminal fragment (CTF), insulin receptor, IGF-1 receptor, glycogen synthase kinase 3-beta (GSK-3beta), protein kinase B (Akt), phosphorylated tau (phospho-tau), synaptophysin, and phosphorylated neurofilaments (SMI-31). RESULTS: Neuronal loss occurred in both models, significantly more so in type 2 diabetic BBZDR/Wor rats compared with type 1 diabetic BB/Wor rats and was associated with a ninefold increase of dystrophic neurites. APP, beta-secretase, beta-amyloid, and CTF were significantly increased in type 2 diabetic rats, as was phospho-tau. The insulin receptor expression was decreased in type 1 diabetes, whereas IGF-1 receptor was decreased in both models, as were Akt and GSK-3beta expression. CONCLUSIONS: The data show that beta-amyloid and phospho-tau accumulation occur in experimental diabetes and that this is associated with neurite degeneration and neuronal loss. The changes were more severe in the type 2 diabetic model and appear to be associated with insulin resistance and possibly hypercholesterolemia. The two models will provide useful tools to unravel further mechanistic associations between diabetes and Alzheimer's disease. Published 28 June 2007 in Diabetes, 56(7): 1817-24.
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