APOE epsilon 4 Increases Risk for Dementia in Pure Synucleinopathies

作者：Tsuang Debby; Leverenz James B; Lopez Oscar L; Hamilton Ronald L; Bennett David A; Schneider Julie A; Buchman Aron S; Larson Eric B; Crane Paul K; Kaye Jeffrey A; Kramer Patricia; Woltjer Randy; Trojanowski John Q; Weintraub Daniel; Chen Plotkin Alice S; Irwin David J; Rick Jacqueline; Schellenberg Gerard D; Watson G Stennis; Kukull Walter; Nelson Peter T; Jicha Gregory A; Neltner Janna H; Galasko Doug; Masliah Eliezer; Quinn Joseph F

来源：JAMA Neurology, 2013, 70(2): 223-228.

DOI：10.1001/jamaneurol.2013.600

Objective: To test for an association between the apolipoprotein E (APOE) epsilon 4 allele and dementias with synucleinopathy. %26lt;br%26gt;Design: Genetic case-control association study. %26lt;br%26gt;Setting: Academic research. %26lt;br%26gt;Patients: Autopsied subjects were classified into 5 categories: dementia with high-level Alzheimer disease (AD) neuropathologic changes (NCs) but without Lewy body disease (LBD) NCs (AD group; n = 244), dementia with LBDNCs and high-level ADNCs (LBD-AD group; n = 224), dementia with LBDNCs and no or low levels of ADNCs (pure DLB [pDLB] group; n = 91), Parkinson disease dementia (PDD) with no or low levels of ADNCs (n = 81), and control group (n = 269). %26lt;br%26gt;Main Outcome Measure: The APOE allele frequencies. %26lt;br%26gt;Results: The APOE e4 allele frequency was significantly higher in the AD (38.1%), LBD-AD (40.6%), pDLB (31.9%), and PDD (19.1%) groups compared with the control group (7.2%; overall chi(2)(4) = 185.25; P = 5.56 X 10(-39)), and it was higher in the pDLB group than the PDD group (P = . 01). In an age-adjusted and sex-adjusted dominant model, epsilon 4 was strongly associated with AD (odds ratio, 9.9; 95% CI, 6.4-15.3), LBD-AD (odds ratio, 12.6; 95% CI, 8.1-19.8), pDLB (odds ratio, 6.1; 95% CI, 3.5-10.5), and PDD (odds ratio, 3.1; 95% CI, 1.7-5.6). %26lt;br%26gt;Conclusions: The APOE epsilon 4 allele is a strong risk factor across the LBD spectrum and occurs at an increased frequency in pDLB relative to PDD. This suggests that epsilon 4 increases the likelihood of presenting with dementia in the context of a pure synucleinopathy. The elevated epsilon 4 frequency in the pDLB and PDD groups, in which the overall brain neuritic plaque burden was low, indicates that apoE might contribute to neurodegeneration through mechanisms unrelated to amyloid processing. JAMA Neurol. 2013;70(2):223-228. Published online November 19, 2012. doi:10.1001/jamaneurol.2013.600

• 出版日期2013-2