Tau phosphorylation pathway genes and cerebrospinal fluid tau levels in Alzheimer's disease.
Tau phosphorylation pathway genes and cerebrospinal fluid tau levels in Alzheimer's disease.
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DOI：
10.1002/ajmg.b.32094
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发表时间：
2012-10
影响因子：
2.8
通讯作者：
Peskind, Elaine R.
中科院分区：
文献类型：
--
作者：
Bekris, Lynn M.;Millard, Steve;Lutz, Franziska;Li, Gail;Galasko, Doug R.;Farlow, Martin R.;Quinn, Joseph F.;Kaye, Jeffrey A.;Leverenz, James B.;Tsuang, Debby W.;Yu, Chang-En;Peskind, Elaine R.
阿尔茨海默病（AD）的特征在于脑中存在主要由淀粉样蛋白β肽（Aβ）组成的淀粉样蛋白斑和主要由tau组成的神经元缠结。过度磷酸化的-tau（p-tau）有助于神经元损伤，并且与认知正常对照相比，AD脑脊液（CSF）中的p-tau和总-tau（t-tau）水平均升高。我们的假设是CSF磷酸化tau水平相对于总tau水平的增加的比率与激酶或磷酸酶基因的调节区遗传变异相关，所述激酶或磷酸酶基因与tau的磷酸化状态生物学相关。选择5个激酶基因和4个磷酸酶基因的5′和3′区域内的18个SNP以及MAPT基因调控区内的2个SNP进行分析。研究样本包括101名AD患者和169名认知正常对照。FYN激酶基因中的Rs7768046和PPP 2 R4磷酸酶基因中的rs 913275均与AD中的CSF p-tau和t-tau水平相关。与对照相比，这些SNP还与AD中相对于t-tau水平的CSF t-tau（rs7768046）或CSF p-tau（rs 913275）差异相关。这些结果表明，rs7768046和rs 913275都以AD相关的方式影响CSF tau水平。
Alzheimer’s disease (AD) is characterized by the presence in the brain of amyloid plaques, consisting predominately of the amyloid β peptide (Aβ), and neurofibrillary tangles, consisting primarily of tau. Hyper-phosphorylated-tau (p-tau) contributes to neuronal damage, and both p-tau and total-tau (t-tau) levels are elevated in AD cerebrospinal fluid (CSF) compared to cognitively normal controls. Our hypothesis was that increased ratios of CSF phosphorylated-tau levels relative to total-tau levels correlate with regulatory region genetic variation of kinase or phosphatase genes biologically associated with the phosphorylation status of tau. Eighteen SNPs located within 5′ and 3′ regions of 5 kinase and 4 phosphatase genes, as well as two SNPs within regulatory regions of the MAPT gene were chosen for this analysis. The study sample consisted of 101 AD patients and 169 cognitively normal controls. Rs7768046 in the FYN kinase gene and rs913275 in the PPP2R4 phosphatase gene were both associated with CSF p-tau and t-tau levels in AD. These SNPs were also differentially associated with either CSF t-tau (rs7768046) or CSF p-tau (rs913275) relative to t-tau levels in AD compared to controls. These results suggest that rs7768046 and rs913275 both influence CSF tau levels in an AD-associated manner.
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DOI：
10.1097/01.wad.0000194014.43575.fd
发表时间：
2005-10-01
影响因子：
2.1
作者：
Peskind, ER;Riekse, R;Galasko, D
通讯作者：
Galasko, D
影响因子：
4
作者：
Qian, Wei;Shi, Jianhua;Liu, Fei
通讯作者：
Liu, Fei
影响因子：
1.5
作者：
SatoHarada，R;Okabe，S;Hirokawa，N
通讯作者：
Hirokawa，N
DOI：
10.1523/jneurosci.4152-10.2011
发表时间：
2011-01-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Roberson ED;Halabisky B;Yoo JW;Yao J;Chin J;Yan F;Wu T;Hamto P;Devidze N;Yu GQ;Palop JJ;Noebels JL;Mucke L
通讯作者：
Mucke L
编码UCSC基因组浏览器中的全基因组数据。
影响因子：
14.9
作者：
Rosenbloom KR;Dreszer TR;Pheasant M;Barber GP;Meyer LR;Pohl A;Raney BJ;Wang T;Hinrichs AS;Zweig AS;Fujita PA;Learned K;Rhead B;Smith KE;Kuhn RM;Karolchik D;Haussler D;Kent WJ
通讯作者：
Kent WJ