Association of glucocerebrosidase mutations with dementia with lewy bodies.
Association of glucocerebrosidase mutations with dementia with lewy bodies.
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DOI：
10.1001/archneurol.2009.54
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发表时间：
2009-05
影响因子：
--
通讯作者：
Marder, Karen
中科院分区：
文献类型：
--
作者：
Clark, Lorraine N.;Kartsaklis, Lykourgos A.;Gilbert, Rebecca Wolf;Dorado, Beatriz;Ross, Barbara M.;Kisselev, Sergey;Verbitsky, Miguel;Mejia-Santana, Helen;Cote, Lucien J.;Andrews, Howard;Vonsattel, Jean-Paul;Fahn, Stanley;Mayeux, Richard;Honig, Lawrence S.;Marder, Karen
葡萄糖脑苷脂酶（GBA）基因突变与路易体（LB）疾病相关。目的探讨GBA基因突变和APOE 4基因型与阿尔茨海默病（AD）及LB的关系。病例对照研究。学术研究。187名受试者包括具有或不具有AD改变的LB疾病的主要神经病理学诊断的患者（95例）、随机选择的AD患者（没有显著的LB病理学发现; 60例）和既没有LB也没有AD病理学发现的对照（32例）。GBA突变状态、APOE 4基因型、LB病理学发现（根据路易体痴呆协会第三份报告评估）和阿尔茨海默病斑块和缠结病理学发现（根据Braak和Braak、阿尔茨海默病登记协会和国家老龄化研究所-里根研究所的标准评定）。在所有受试者中，18%（34/187）发现了GBA突变，包括28%（27/95）的原发性LB病理结果，而AD病理结果为10%（6/60），无AD或LB病理结果为3%（1/32）（P= 0.001）。在校正性别、死亡年龄和APOE 4后，GBA突变状态与皮质LB的存在显著相关（比值比，6.48; 95%置信区间，2.45-17.16; P<0.001）。在调整性别、死亡年龄和APOE 4后，GBA突变携带者符合AD病理诊断（国家老龄化研究所-里根研究所中等或高可能性）标准的可能性显著降低（比值比，0.35; 95%置信区间，0.15-0.79; P= 0.01）。GBA突变可能与病理学上“更纯”的LB疾病相关，其特征在于更广泛的（皮质）LB和不太严重的AD病理学发现，并且可能是LB疾病的有用标志物。
Mutations in the glucocerebrosidase (GBA) gene are associated with Lewy body (LB) disorders. To determine the relationship of GBA mutations and APOE4 genotype to LB and Alzheimer disease (AD) pathological findings. Case-control study. Academic research. The 187 subjects included patients with primary neuropathological diagnoses of LB disorders with or without AD changes (95 cases), randomly selected patients with AD (without significant LB pathological findings; 60 cases), and controls with neither LB nor AD pathological findings (32 cases). GBA mutation status, APOE4 genotype, LB pathological findings (assessed according to the third report of the Dementia With Lewy Body Consortium), and Alzheimer plaque and tangle pathological findings (rated by criteria of Braak and Braak, the Consortium to Establish a Registry for Alzheimer Disease, and the National Institute on Aging–Reagan Institute). GBA mutations were found in 18% (34 of 187) of all subjects, including 28% (27 of 95) of those with primary LB pathological findings compared with 10% (6 of 60) of those with AD pathological findings and 3% (1 of 32) of those without AD or LB pathological findings (P=.001). GBA mutation status was significantly associated with the presence of cortical LBs (odds ratio, 6.48; 95% confidence interval, 2.45–17.16; P<.001), after adjusting for sex, age at death, and presence of APOE4. GBA mutation carriers were significantly less likely to meet AD pathological diagnostic (National Institute on Aging–Reagan Institute intermediate or high likelihood) criteria (odds ratio, 0.35; 95% confidence interval, 0.15–0.79; P=.01) after adjustment for sex, age at death, and APOE4. GBA mutations may be associated with pathologically “purer” LB disorders, characterized by more extensive (cortical) LB, and less severe AD pathological findings and may be a useful marker for LB disorders.
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影响因子：
8.6
作者：
Clark, LN;Nicolai, A;Marder, K
通讯作者：
Marder, K
影响因子：
9.9
作者：
Clark, L. N.;Ross, B. M.;Marder, K.
通讯作者：
Marder, K.
影响因子：
9.9
作者：
Goker-Alpan, O.;Giasson, B. I.;Sidransky, E.
通讯作者：
Sidransky, E.
影响因子：
9.9
作者：
Toft, M;Pielsticker, L;Farrer, MJ
通讯作者：
Farrer, MJ
影响因子：
--
作者：
Mata, Ignacio F.;Samii, Ali;Zabetian, Cyrus P.
通讯作者：
Zabetian, Cyrus P.