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Arch Neurol:APOE4基因与帕金森病痴呆相关

来源:医脉通 2012-11-23 22:41

最近一项研究提示载脂蛋白E(APOE)ε4等位基因可能是帕金森病(PD)痴呆和其他突触核蛋白病的一个风险因素。而之前的研究发现APOEε4等位基因通过影响淀粉样蛋白-β代谢从而与阿尔茨海默病(AD)相关联。这一研究结果在线发表在11月19日的《神经病学年鉴》杂志上。

研究人员发现,AD患者以及路易体痴呆型AD(LBD-AD)患者,PD痴呆(PDD)患者和单纯路易体(pDLB)痴呆患者均存在ε4等位基因高度过表达。APOEε4可能通过淀粉样蛋白加工机制来促成神经退行性病变。

西雅图华盛顿大学精神病学和行为科学部的Debby Tsuang博士及其同事们称,“虽然ε4等位基因是一种已确定的AD风险因素,且一些研究报道了APOE和LBD-AD之间存在关联,但APOEε4在pDLB和PDD中过表达令人意外” 。

在这项研究中,研究人员通过对死亡患者尸检对APOE进行了基因分型,其中AD244例,LBD-AD224例,pDLB 91例,或PDD 81例,以及对照者(认知正常的老年人)269例。同时,从外周血白细胞或脑组织中提取DNA,通过基因分型来区分APOEε2, ε3 及ε4等位基因。

研究人员发现,所有病例组包括PDD和pDLB在内,ε4等位基因明显过表达。在突触核蛋白病患者组中,PDD患者的ε4等位基因出现频率(19%)明显较pDLB(31.9%)或LBD-AD(40.6%)低。(生物谷Bioon.com)

Neuropathologic substrates of Parkinson disease dementia

Irwin DJ, White MT, Toledo JB, Xie SX, Robinson JL, Van Deerlin V, Lee VM, Leverenz JB, Montine TJ, Duda JE, Hurtig HI, Trojanowski JQ.

OBJECTIVE: A study was undertaken to examine the neuropathological substrates of cognitive dysfunction and dementia in Parkinson disease (PD). METHODS: One hundred forty patients with a clinical diagnosis of PD and either normal cognition or onset of dementia 2 or more years after motor symptoms (PDD) were studied. Patients with a clinical diagnosis of dementia with Lewy bodies were excluded. Autopsy records of genetic data and semiquantitative scores for the burden of neurofibrillary tangles, senile plaques, Lewy bodies (LBs), and Lewy neurites (LNs) and other pathologies were used to develop a multivariate logistic regression model to determine the independent association of these variables with dementia. Correlates of comorbid Alzheimer disease (AD) were also examined. RESULTS: Niney-two PD patients developed dementia, and 48 remained cognitively normal. Severity of cortical LB (CLB)/LN pathology was positively associated with dementia (p < 0.001), with an odds ratio (OR) of 4.06 (95% confidence interval [CI], 1.87-8.81), as was apolipoprotein E4 (APOE4) genotype (p = 0.018; OR, 4.19; 95% CI, 1.28-13.75). A total of 28.6% of all PD cases had sufficient pathology for comorbid AD, of whom 89.5% were demented. The neuropathological diagnosis of PDD+AD correlated with an older age of PD onset (p = 0.001; OR, 1.12; 95% CI, 1.04-1.21), higher CLB/LN burden (p = 0.037; OR, 2.48; 95% CI, 1.06-5.82), and cerebral amyloid angiopathy severity (p = 0.032; OR, 4.16; 95% CI, 1.13-15.30). INTERPRETATION: CLB/LN pathology is the most significant correlate of dementia in PD. Additionally, APOE4 genotype may independently influence the risk of dementia in PD. AD pathology was abundant in a subset of patients, and may modify the clinical phenotype. Thus, therapies that target α-synuclein, tau, or amyloid β could potentially improve cognitive performance in PD.

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