Alzheimer-like changes in rat models of spontaneous diabetes.
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.


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.
Li
Zhen-guo
ZG
Department of Pathology, Wayne State University, School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA.
Zhang
Weixian
W
Sima
Anders A F
AA
D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D048909:Diabetes Complications; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004195:Disease Models, Animal; D008297:Male; D009474:Neurons / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains