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Diabetes. 2007 Jul;56(7):1817-24. Epub 2007 Apr 24.

Alzheimer-like changes in rat models of spontaneous diabetes.

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  • 1Department of Pathology, Wayne State University, School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA.

Erratum in

  • Diabetes. 2007 Oct;56(10):2650.



To examine whether changes characteristic of Alzheimer's disease occur in two rat models with spontaneous onset of type 1 and type 2 diabetes.


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).


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.


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.

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