最近一項(xiàng)研究提示載脂蛋白E（APOE)ε4等位基因可能是帕金森?。≒D）癡呆和其他突觸核蛋白病的一個(gè)風(fēng)險(xiǎn)因素,。而之前的研究發(fā)現(xiàn)APOEε4等位基因通過(guò)影響淀粉樣蛋白-β代謝從而與阿爾茨海默病（AD）相關(guān)聯(lián),。這一研究結(jié)果在線發(fā)表在11月19日的《神經(jīng)病學(xué)年鑒》雜志上,。
研究人員發(fā)現(xiàn)，AD患者以及路易體癡呆型AD（LBD-AD）患者,，PD癡呆（PDD）患者和單純路易體（pDLB）癡呆患者均存在ε4等位基因高度過(guò)表達(dá),。APOEε4可能通過(guò)淀粉樣蛋白加工機(jī)制來(lái)促成神經(jīng)退行性病變。
西雅圖華盛頓大學(xué)精神病學(xué)和行為科學(xué)部的Debby Tsuang博士及其同事們稱,，“雖然ε4等位基因是一種已確定的AD風(fēng)險(xiǎn)因素,，且一些研究報(bào)道了APOE和LBD-AD之間存在關(guān)聯(lián)，但APOEε4在pDLB和PDD中過(guò)表達(dá)令人意外” ,。
在這項(xiàng)研究中,，研究人員通過(guò)對(duì)死亡患者尸檢對(duì)APOE進(jìn)行了基因分型，其中AD244例,，LBD-AD224例,，pDLB 91例，或PDD 81例,，以及對(duì)照者（認(rèn)知正常的老年人）269例,。同時(shí)，從外周血白細(xì)胞或腦組織中提取DNA,，通過(guò)基因分型來(lái)區(qū)分APOEε2, ε3 及ε4等位基因,。
研究人員發(fā)現(xiàn)，所有病例組包括PDD和pDLB在內(nèi),，ε4等位基因明顯過(guò)表達(dá),。在突觸核蛋白病患者組中，PDD患者的ε4等位基因出現(xiàn)頻率（19％）明顯較pDLB（31.9％）或LBD-AD（40.6％）低,。（生物谷Bioon.com）
doi: 10.1002/ana.23659
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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.
