Plasma levels of apolipoprotein E and risk of dementia in the general population
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Plasma levels of apolipoprotein E and risk of dementia in the general population. / Rasmussen, Katrine L.; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G; Frikke-Schmidt, Ruth.
In: Annals of Neurology, Vol. 77, No. 2, 02.2015, p. 301-11.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Plasma levels of apolipoprotein E and risk of dementia in the general population
AU - Rasmussen, Katrine L.
AU - Tybjaerg-Hansen, Anne
AU - Nordestgaard, Børge G
AU - Frikke-Schmidt, Ruth
N1 - © 2014 American Neurological Association.
PY - 2015/2
Y1 - 2015/2
N2 - OBJECTIVE: The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and dementia. However, it remains unclear whether plasma levels of apoE confer additional risk. We tested this hypothesis.METHODS: Using 75,708 participants from the general population, we tested whether low plasma levels of apoE at study enrollment were associated with increased risk of future Alzheimer disease and all dementia, and whether this association was independent of ε2/ε3/ε4 APOE genotype.RESULTS: Multifactorially adjusted hazard ratios (HRs) for Alzheimer disease and all dementia increased from the highest to the lowest apoE tertile (p for trends < 1 × 10(-6) ). Multifactorially adjusted HRs for lowest versus highest tertile were 2.68 (95% confidence interval [CI] = 2.04-3.52) and 1.80 (95% CI = 1.52-2.13) for Alzheimer disease and all dementia, respectively. After further adjustment for ε2/ε3/ε4 APOE genotype, plasma apoE tertiles remained associated with Alzheimer disease (p for trend = 0.007) and all dementia (p for trend = 0.04). Plasma apoE tertiles did not interact with ε2/ε3/ε4 APOE genotype on risk of Alzheimer disease (p = 0.53) or all dementia (p = 0.79). In a subanalysis, the -219G>T GT promoter genotype, associated with low plasma apoE levels, remained significantly associated with increased risk of Alzheimer disease after adjustment for ε2/ε3/ε4 APOE genotype (HR = 1.56, 95% CI = 1.05-2.30).INTERPRETATION: Low plasma levels of apoE are associated with increased risk of future Alzheimer disease and all dementia in the general population, independent of ε2/ε3/ε4 APOE genotype. This is clinically relevant, because no plasma biomarkers are currently implemented. Hence, plasma levels of apoE may be a new, easily accessible preclinical biomarker.
AB - OBJECTIVE: The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and dementia. However, it remains unclear whether plasma levels of apoE confer additional risk. We tested this hypothesis.METHODS: Using 75,708 participants from the general population, we tested whether low plasma levels of apoE at study enrollment were associated with increased risk of future Alzheimer disease and all dementia, and whether this association was independent of ε2/ε3/ε4 APOE genotype.RESULTS: Multifactorially adjusted hazard ratios (HRs) for Alzheimer disease and all dementia increased from the highest to the lowest apoE tertile (p for trends < 1 × 10(-6) ). Multifactorially adjusted HRs for lowest versus highest tertile were 2.68 (95% confidence interval [CI] = 2.04-3.52) and 1.80 (95% CI = 1.52-2.13) for Alzheimer disease and all dementia, respectively. After further adjustment for ε2/ε3/ε4 APOE genotype, plasma apoE tertiles remained associated with Alzheimer disease (p for trend = 0.007) and all dementia (p for trend = 0.04). Plasma apoE tertiles did not interact with ε2/ε3/ε4 APOE genotype on risk of Alzheimer disease (p = 0.53) or all dementia (p = 0.79). In a subanalysis, the -219G>T GT promoter genotype, associated with low plasma apoE levels, remained significantly associated with increased risk of Alzheimer disease after adjustment for ε2/ε3/ε4 APOE genotype (HR = 1.56, 95% CI = 1.05-2.30).INTERPRETATION: Low plasma levels of apoE are associated with increased risk of future Alzheimer disease and all dementia in the general population, independent of ε2/ε3/ε4 APOE genotype. This is clinically relevant, because no plasma biomarkers are currently implemented. Hence, plasma levels of apoE may be a new, easily accessible preclinical biomarker.
KW - Aged
KW - Apolipoproteins E
KW - Biomarkers
KW - Dementia
KW - Denmark
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Male
KW - Middle Aged
KW - Population Surveillance
KW - Prospective Studies
KW - Risk Factors
U2 - 10.1002/ana.24326
DO - 10.1002/ana.24326
M3 - Journal article
C2 - 25469919
VL - 77
SP - 301
EP - 311
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 2
ER -
ID: 161441589