Genetic Discoveries in AD Using CSF Amyloid and Tau

被引：0
作者：
Carlos Cruchaga
Mark T. W. Ebbert
John S. K. Kauwe
机构：
[1] Washington University School of Medicine,Department of Psychiatry
[2] Washington University School of Medicine,The Hope Center Program on Protein Aggregation and Neurodegeneration (HPAN)
[3] Brigham Young University,Department of Biology, 673 WIDB
[4] The ARUP Institute for Clinical and Experimental Pathology,Department of Biology, 675 WIDB
[5] BJC Institute of Health,undefined
[6] Brigham Young University,undefined
来源：
Current Genetic Medicine Reports | 2014年 / 2卷 / 1期
关键词：
Cerebrospinal fluid; Abeta; Tau; Alzheimer’s disease; Endophenotype; GWAS;
D O I：
10.1007/s40142-014-0031-0
中图分类号：
学科分类号：
摘要：
The use of cerebrospinal fluid (CSF) levels of Aβ42 and Tau phosphorylated at threonine 181 (pTau181) as endophenotypes for genetic studies of Alzheimer’s disease (AD) has led to successful identification of both rare and common AD risk variants. In addition, this approach has provided meaningful hypotheses for the biological mechanisms by which known AD risk variants modulate the disease process. In this article, we discuss these successes and outline challenges to effective and continued applications of this approach. We contrast the statistical power of this approach with traditional case-control designs and discuss solutions to address challenges in quality control and data analysis for these phenotypes. Finally, we discuss the potential for the use of this approach with larger samples as well as the incorporation of next generation sequencing and for future work with other endophenotypes for AD.
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页码：23 / 29
页数：6
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  • [1] Gottesman II(1973)Genetic theorizing and schizophrenia Br J Psychiatry 122 15-30
  • [2] Shields J(2003)The endophenotype concept in psychiatry: etymology and strategic intentions Am J Psychiatry 160 636-645
  • [3] Gottesman II(1986)Clinical methods in psychiatric genetics. I. Robustness of genetic marker investigative strategies Acta Psychiatr Scand 74 113-118
  • [4] Gould TD(2012)Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5 BMC Genet 13 12-349
  • [5] Gershon ES(2010)Intermediate phenotypes identify divergent pathways to Alzheimer’s disease PLoS ONE 5 e11244-320
  • [6] Goldin LR(2007)Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults Arch Neurol 64 343-173
  • [7] Nolan DK(2007)Prediction of Alzheimer’s disease using the CSF Abeta42/Abeta40 ratio in patients with mild cognitive impairment Dement Geriatr Cogn Disord 23 316-453
  • [8] Sutton B(2007)Cerebrospinal fluid tau, phospho-tau181 and beta-amyloid1-42 in idiopathic normal pressure hydrocephalus: a discrimination from Alzheimer’s disease Eur J Neurol 14 168-1055
  • [9] Haynes C(2007)Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer’s disease presenilin 1 mutation Ann Neurol 61 446-883
  • [10] Shulman JM(2007)Clinicopathological concordance and discordance in three monozygotic twin pairs with familial Alzheimer’s disease J Neurol Neurosurg Psychiatry 78 1050-79
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