Association of MAPT haplotype-tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort.
Association of MAPT haplotype-tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort.
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DOI：
10.1002/brb3.1128
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发表时间：
2018-11
影响因子：
3.1
通讯作者：
Šimić G
中科院分区：
文献类型：
--
作者：
Babić Leko M;Willumsen N;Nikolac Perković M;Klepac N;Borovečki F;Hof PR;Sonicki Z;Pivac N;de Silva R;Šimić G
阿尔茨海默病（AD）是世界上导致痴呆症的主要原因。早期发现阿尔茨海默病对于更快和更有效地使用治疗和预防措施至关重要。尽管已知载脂蛋白E基因的1个ε4等位基因可使散发性AD的发病风险增加5倍，2个ε4等位基因可使散发性AD的发病风险增加20倍，但目前还没有可靠的AD遗传标记。先前的研究表明，微管相关蛋白tau （MAPT）基因多态性可能与阿尔茨海默病风险增加有关。目前的研究包括113名AD患者和53名轻度认知障碍（MCI）患者，以及9名健康对照（HC）和53名其他原发性痴呆患者。该研究评估了6种MAPT单倍型标记多态性（rs1467967、rs242557、rs3785883、rs2471738、德尔- in9和rs7521）和MAPT单倍型是否与AD病理相关，通过脑脊液（CSF） AD生物标志物淀粉样蛋白β1-42 （Aβ1-42）、总tau （t - tau）、表位181 （p‐tau181）、199 （p‐tau199）和231 （p‐tau231）磷酸化的tau和视素样蛋白1 （VILIP‐1）进行测量。AG和AA MAPT rs1467967基因型、CC MAPT rs2471738基因型以及H1H2或H2H2 MAPT单倍型患者的t - tau和p - tau CSF水平显著升高。这些结果表明，MAPT单倍型标记多态性和MAPT单倍型作为AD的潜在遗传生物标志物有待进一步研究。
Alzheimer's disease (AD) is the world leading cause of dementia. Early detection of AD is essential for faster and more efficacious usage of therapeutics and preventive measures. Even though it is well known that one ε4 allele of apolipoprotein E gene increases the risk for sporadic AD five times, and that two ε4 alleles increase the risk 20 times, reliable genetic markers for AD are not yet available. Previous studies have shown that microtubule‐associated protein tau (MAPT) gene polymorphisms could be associated with increased risk for AD. The present study included 113 AD patients and 53 patients with mild cognitive impairment (MCI), as well as nine healthy controls (HC) and 53 patients with other primary causes of dementia. The study assessed whether six MAPT haplotype‐tagging polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, del–In9, and rs7521) and MAPT haplotypes are associated with AD pathology, as measured by cerebrospinal fluid (CSF) AD biomarkers amyloid β1–42 (Aβ1–42), total tau (t‐tau), tau phosphorylated at epitopes 181 (p‐tau181), 199 (p‐tau199), and 231 (p‐tau231), and visinin‐like protein 1 (VILIP‐1). Significant increases in t‐tau and p‐tau CSF levels were found in patients with AG and AA MAPT rs1467967 genotype, CC MAPT rs2471738 genotype and in patients with H1H2 or H2H2 MAPT haplotype. These results indicate that MAPT haplotype‐tagging polymorphisms and MAPT haplotypes should be further tested as potential genetic biomarkers of AD.
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DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
DOI：
10.1073/pnas.0801227105
发表时间：
2008-06-10
影响因子：
11.1
作者：
Kauwe, John S. K.;Cruchaga, Carlos;Goate, Alison M.
通讯作者：
Goate, Alison M.
DOI：
10.1002/ajmg.b.30951
发表时间：
2009-12-05
影响因子：
2.8
作者：
Abraham, Richard;Sims, Rebecca;Owen, Michael J.
通讯作者：
Owen, Michael J.
与阿尔茨海默氏病和脑脊液生物标志物相关的遗传基因座在芬兰病例控制队列中。
影响因子：
3.7
作者：
Elias-Sonnenschein LS;Helisalmi S;Natunen T;Hall A;Paajanen T;Herukka SK;Laitinen M;Remes AM;Koivisto AM;Mattila KM;Lehtimäki T;Verhey FR;Visser PJ;Soininen H;Hiltunen M
通讯作者：
Hiltunen M
影响因子：
9.9
作者：
Chen, Jason;Yu, Jin-Tai;Boxer, Adam L.
通讯作者：
Boxer, Adam L.