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Clinical and Neuropathological Correlates of Apolipoprotein E Genotype in Dementia with Lewy Bodies

Singleton A.B.a,1,2 · Wharton A.a,1 · O’Brien K.K.a,d · Walker M.P.a · McKeith I.G.b · Ballard C.G.a,b · O’Brien J.a,b · Perry R.H.c · Ince P.G.a,c,3 · Edwardson J.A.a · Morris C.M.a,d
aMedical Research Council/University of Newcastle upon Tyne, Centre Development in Clinical Brain Ageing, MRC Building, bDepartment of Old Age Psychiatry, cDepartment of Neuropathology, Institute for Ageing and Health, Newcastle General Hospital, and dInstitute for Human Genetics, International Centre for Life, Newcastle upon Tyne, UK Dement Geriatr Cogn Disord 2002;14:167–175 (DOI:10.1159/000066022)

Abstract

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) ε4 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 ε4 allele in a large series of DLB cases coming to autopsy to: (1) determine if the ε4 allele describes a similar risk in DLB development as in AD and (2) determine how APO E ε4 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 ε4 allele frequency, though in DLB the ε2 allele frequency is not reduced and there is a relative lack of ε4 homozygotes. In contrast to previous studies, no association of the ε4 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 ε4 allele on disease onset or duration was seen. The survival rate was reduced by the presence of the ε4 allele in DLB, as with AD. No effect on SP or NFT counts was seen with the ε4 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 ε4 allele with AD as a common risk factor, but that there are differences in the way the ε4 allele affects the phenotypic expression of disease.

 

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