β‐Amyloid deposition in brains of subjects with diabetes
- 21 January 2009
- journal article
- Published by Wiley in Neuropathology and Applied Neurobiology
- Vol. 35 (1), 60-68
- https://doi.org/10.1111/j.1365-2990.2008.00948.x
Abstract
A causative association between diabetes mellitus (DM) and Alzheimer's disease (AD) has been suggested based on clinical and epidemiological studies. One hypothesis is that the link between DM and AD is related to the function of insulin-degrading enzyme (IDE), an enzyme that degrades not only insulin and pancreatic amylin but also beta-amyloid (Abeta). Thus, in diabetics, insulin and Abeta might compete for IDE and this might lead to an increase in Abeta. The objective of this study was to test the hypothesis that hyperinsulinaemia can elevate Abeta levels and thus contribute to AD pathology in humans. Neuropathological examination was carried out employing conventional and immunohistochemical (IHC) methods of the brains obtained post mortem from 701 aged subjects. The loads of IHC/Abeta, silver stained neuritic plaques (NP) and neurofibrillary tangles (NFT) were significantly higher in subjects carrying the Apolipoprotein E e4 allele. In contrast, the loads of Abeta, NPs and NFT in the brains were not influenced by hyperglycaemia when comparing 134 diabetic with 567 non-diabetic subjects. We conclude that the hypothesis that hyperinsulinaemia would significantly elevate the Abeta load and thus increase the extent of AD pathology cannot be supported. Our result challenges the claim that DM is a direct risk factor of developing AD. Thus further studies on pathological lesions in demented diabetics should be conducted.Keywords
This publication has 30 references indexed in Scilit:
- Impairment of Skin Capillary Recruitment Precedes Chronic Complications in Patients with Type 1 DiabetesThe Review of Diabetic Studies, 2007
- Insulin, insulin-degrading enzyme and amyloid-β peptide in Alzheimer's disease: review and hypothesisNeurobiology of Aging, 2006
- Does insulin dysfunction play a role in Alzheimer's disease?Trends in Pharmacological Sciences, 2002
- The genetics of late-onset Alzheimerʼs diseaseCurrent Opinion in Neurology, 2001
- A Major Locus for Fasting Insulin Concentrations and Insulin Resistance on Chromosome 6q with Strong Pleiotropic Effects on Obesity-Related Phenotypes in Nondiabetic Mexican AmericansAmerican Journal of Human Genetics, 2001
- Evidence for Genetic Linkage of Alzheimer's Disease to Chromosome 10qScience, 2000
- β-Amyloid Load Is Not Influenced by the Severity of Cardiovascular Disease in Aged and Demented PatientsStroke, 1999
- Effect of glucose, glucose regulation, and word imagery value on human memory.Behavioral Neuroscience, 1999
- A longitudinal study of cognitive performance in noninsulin dependent (type II) diabetic menExperimental Gerontology, 1986
- Cognitive Processes in Insulin-dependent DiabetesDiabetes Care, 1984