Beta-amyloid deposition in brains of subjects with diabetes.
OBJECTIVE
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.


METHODS
Neuropathological examination was carried out employing conventional and immunohistochemical (IHC) methods of the brains obtained post mortem from 701 aged subjects.


RESULTS
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.


CONCLUSIONS
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.
Alafuzoff
I
I
Unit of Neurology, Department of Clinical Medicine, Kuopio University and Kuopio University Hospital, Kuopio, Finland. irina.alafuzoff@uku.fi
Aho
L
L
Helisalmi
S
S
Mannermaa
A
A
Soininen
H
H
D000368:Aged; D000483:Alleles; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D020520:Brain Infarction / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology; D003704:Dementia / Q000235:genetics / Q000473:pathology; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4