Clinical and neuropathological correlates of apolipoprotein E genotype in dementia with Lewy bodies.
Dementia with Lewy bodies (DLB) represents the second commonest cause of dementia in the elderly following Alzheimer's disease (AD). Whilst the presence of Lewy bodies is essential, DLB shares with AD the presence of senile plaques (SP), but neurofibrillary tangles (NFT) are not a necessary feature. The apolipoprotein E (APO E) epsilon4 allele is the most consistently associated genetic risk factor for AD and has also been shown to associate with DLB. We have therefore analysed the APO E epsilon4 allele in a large series of DLB cases coming to autopsy to: (1) determine if the epsilon4 allele describes a similar risk in DLB development as in AD and (2) determine how APO E epsilon4 allele status correlates with clinical and neuropathological findings in DLB, and in AD, as an indication of the role of APO E in underlying disease biology. Both DLB and AD share an increased epsilon4 allele frequency, though in DLB the epsilon2 allele frequency is not reduced and there is a relative lack of epsilon4 homozygotes. In contrast to previous studies, no association of the epsilon4 allele with age at onset or duration of disease was found in either disorders. In DLB cases, overall a significantly shorter duration of illness was observed when compared with AD cases, though no significant effect of the epsilon4 allele on disease onset or duration was seen. The survival rate was reduced by the presence of the epsilon4 allele in DLB, as with AD. No effect on SP or NFT counts was seen with the epsilon4 allele, though DLB cases showed a lower SP burden in addition to the expected lower NFT counts. This study demonstrates that DLB shares the APO epsilon4 allele with AD as a common risk factor, but that there are differences in the way the epsilon4 allele affects the phenotypic expression of disease.
Singleton
Andrew B
AB
Medical Research Council/University of Newcastle upon Tyne, Centre Development in Clinical Brain Ageing, MRC Building, Newcastle upon Tyne, UK.
Wharton
Anna
A
O'Brien
Kirsty K
KK
Walker
Matthew P
MP
McKeith
Ian G
IG
Ballard
Clive G
CG
O'Brien
John
J
Perry
Robert H
RH
Ince
Paul G
PG
Edwardson
James A
JA
Morris
Christopher M
CM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged
D053327:Apolipoprotein E4; D001057:Apolipoproteins E