Apolipoprotein E ε2 allele promotes longevity and protects... : NeuroReport (original) (raw)

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Apolipoprotein E ε2 allele promotes longevity and protects patients with Down's syndrome from dementia

Royston, M. Claire; Mann, David1; Pickering-Brown, Stuart1; Owen, Frank1; Perry, Robert2; Raghavan, Ravi2; Khin-IMu, Claire3; Tyrer, Stephen3; Day, Kenneth3; Crook, Richard4; Hardy, John4; Roberts, Gareth W.5

Departments of Psychiatry and Anatomy, Charing Cross and Westminster Medical School, London W6 8RP;

1Department of Pathological Sciences and Neuroscience, University of Manchester, Manchester M13 9PT;

2Department of Neuropathology, MRC Neurochemical Pathology Unit and Institute of Health for the Elderly, Newcastle General Hospital, Newcastle Upon Tyne NE4 6BE;

3Department of Psychiatry, Northgate and Prudhoe NHS Trust Hospital, Morpeth, Northumberland NE61 3BP, UK;

4Suncoast Alzheimer's Disease Laboratories, Departments of Psychiatry, Pharmacology, Neurology and Biochemistry, 3515 E. Fletcher Ave, University of South Florida, MDC14, Tampa, FL33613, USA;

5Department of Molecular Neuropathology, SmithKline Beecham Pharmaceuticals, Harlow CM195AD, UK

Abstract

ALTHOUGH individuals with Down's syndrome nearly always develop the clinical and pathological features of Alzheimer's disease, some clearly do not become demented despite living into their sixth and seventh decades. Genetic variation at the apolipoprotein E locus has recently been shown to be an important determinant of Alzheimer's disease, with the ε4 allele having been shown to be associated with the disease and, at least in some cases, the ε2 allele being negatively associated with the disease. Here we show, in a series of clinically assessed individuals with Down's syndrome, that the ε2 allele of ApoE is associated with both longevity and the absence of clinical evidence of dementia. These data show that the clinical phenotype of Down's syndrome can be modulated by genes on chromosomes other than chromosome 21. The importance of this observation to the pathogenesis of Alzheimer's disease, both in Down's syndrome and in general, is discussed.