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Molecular biology of APO E alleles in Alzheimer's and non-Alzheimer's dementias

Lookup NU author(s): Dr Christopher Morris, Alan Leake, Dr Michael Griffiths, Dr Heather Lamb, Andrew Brown, Dr Stephen Tyrer, Paul Thompson, Professor Ian McKeith, Professor Jim Edwardson, Emeritus Professor Robert Perry, Emeritus Professor Elaine Perry


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Current research into the aetiology of the dementias is focused upon genetic factors which give rise to the disease process. Recently the Apolipoprotein E gene (APO E) and in particular the epsilon 4 allele has been shown to be a risk factor for late onset Alzheimer's disease (AD) where there is an increased frequency of the epsilon 4 allele. The epsilon 4 allele has also been shown to reduce the age at onset of dementia in AD in a dose dependant manner, with the epsilon 2 allele having an opposing effect. We have genotyped a large series of clinically and neuropathologically confirmed cases of AD and found the expected increase in the Apolipoprotein epsilon 4 allele frequency when compared to a control population. Similarly, in Lewy Body Dementia (LED) an increased epsilon 4 frequency is also found though a normal epsilon 2 frequency exists, unlike in AD where the epsilon 2 frequency is reduced. No changes in APO E allele frequencies were found in presenile AD, Parkinson's disease with or without dementia, or in Down's syndrome. No association was found between any of the APO E alleles and the histopathological indices of AD, cortical senile plaques and neurofibrillary tangles, in any disease category. Neurochemical indicators of AD, loss of choline acetyltransferase activity was also unaffected by APO E genotype. Whilst their appears to be a strong association between the APO E allele and AD and also in LED, other related neurodegenerative disorders associated with dementia do not show such a linkage. Changes in the epsilon 2 allele frequency may indicate a genetic difference between AD and LED. The epsilon 4 allele does not appear to influence the burden of AD type pathology and this is particularly relevant given the relative lack of NFT in LED indicating that factors other than SP or NFT may govern the onset of dementia.

Publication metadata

Author(s): Tyrer S; McKeith IG; Thompson P; Edwardson JA; Perry RH; Leake A; Perry EK; Morris CM; Massey HM; Benjamin R; Broadbent C; Griffiths M; Lamb H; Brown A; Ince PG

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Meeting on New Trends in the Diagnosis and Therapy of Non-Alzheimer's Dementia

Year of Conference: 1996

Pages: 205-218

ISSN: 0303-6995

Publisher: Springer Wien

Library holdings: Search Newcastle University Library for this item

Series Title: Journal of Neural Transmission Supplement