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Parental history of Alzheimer disease associated with lower plasma apolipoprotein E levels

From the Department of Gerontology and Geriatrics (P.v.V., R.G.J.W.), Department of Clinical Chemistry (M.F.), and Department of Clinical Genetics, Center for Human and Clinical Genetics (E.B.), Leiden University Medical Center; Department of Psychiatry (P.E., H.C.C., E.v.E.), VU Medical Center/SGB, Amsterdam; Department of Neurology (P.E.), Academic Medical Center, Amsterdam; and Department of Neurology (W.v.d.F.), VU Medical Center, Amsterdam, The Netherlands.

Address correspondence and reprint requests to Dr. P. van Vliet, Leiden University Medical Center, Department of Gerontology and Geriatrics (C2-R), PO Box 9600, 2300 RC, Leiden, The Netherlands p.van_vliet{at}lumc.nl

Background: Variation in APOE genotype is a determinant of Alzheimer disease (AD), but the risk associated with variation in plasma apoE levels has yet to be determined. Here, we studied offspring with and without a parental history of AD to identify the effect of plasma apoE levels at middle age on the risk of late-onset AD.

Methods: Some 203 offspring from 92 families with a parental history of AD were compared with 197 offspring from 97 families without a parental history of AD. APOE genotypes and plasma apoE levels were assessed in all offspring. Difference in plasma apoE level between subjects with and without a parental history of AD was calculated using robust linear regression, both stratified and adjusted for APOE genotype.

Results: Offspring with a parental history of AD were more likely to be an APOE 4 allele carrier (46% vs 21%, p < 0.001) than offspring without such a parental history. Mean plasma apoE levels strongly decreased from 2 to 33 to 4 carriers (p < 0.001). Offspring with a parental history of AD had lower plasma apoE levels than subjects without such a history, both in analyses adjusted for APOE genotype (difference: –0.21 mg/dL, p = 0.02) and when using standardized Z scores, when stratified for APOE genotype (difference: –0.22, p = 0.009).

Conclusions: Our findings suggest that lower plasma apoE levels in middle age could be a risk factor for Alzheimer disease in old age, independent of APOE genotype.

Abbreviations: AD = Alzheimer disease; BMI = body mass index; CI = confidence interval; CVD = cardiovascular disease; EOAD = early-onset Alzheimer disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein; LOAD = late-onset Alzheimer disease; MMSE = Mini-Mental State Examination; VaD = vascular dementia.

Supported by grants from the National Institute of Aging, USA (R03 AG 276163-01), the EU project LifeSpan (LSHG-CT-2007-036894), and the Internationale Stichting Alzheimer Onderzoek (International Foundation for Alzheimer Research, The Netherlands).

Disclosure: Author disclosures are provided at the end of the article.

Received March 5, 2009. Accepted in final form June 5, 2009.