{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:40:13Z","timestamp":1791031213021,"version":"4.1.0"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2010,9,23]],"date-time":"2010-09-23T00:00:00Z","timestamp":1285200000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"DOI":"10.1371\/journal.pgen.1001130","type":"journal-article","created":{"date-parts":[[2010,9,23]],"date-time":"2010-09-23T19:38:19Z","timestamp":1285270699000},"page":"e1001130","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":118,"title":["Dementia Revealed: Novel Chromosome 6 Locus for Late-Onset Alzheimer Disease Provides Genetic Evidence for Folate-Pathway Abnormalities"],"prefix":"10.1371","volume":"6","author":[{"given":"Adam C.","family":"Naj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary W.","family":"Beecham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eden R.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Gallins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric H.","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Konidari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice L.","family":"Whitehead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqing","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahram","family":"Haroutunian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William K.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery M.","family":"Vance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Slifer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry E.","family":"Gwirtsman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Gilbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan L.","family":"Haines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Buxbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Pericak-Vance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2010,9,23]]},"reference":[{"key":"ref1","article-title":"2009 Alzheimer's Disease Facts and Figures.","year":"2009"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1001\/archneur.60.8.1119","article-title":"Alzheimer disease in the US population: prevalence estimates using the 2000 census.","volume":"60","author":"LE Hebert","year":"2003","journal-title":"Arch Neurol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/349704a0","article-title":"Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.","volume":"349","author":"A Goate","year":"1991","journal-title":"Nature"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/375754a0","article-title":"Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.","volume":"375","author":"R Sherrington","year":"1995","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1002\/ana.410380420","article-title":"Apolipoprotein E genotypes and age of onset in early-onset familial Alzheimer's disease.","volume":"38","author":"E Levy-Lahad","year":"1995","journal-title":"Ann Neurol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1126\/science.7638622","article-title":"Candidate gene for the chromosome 1 familial Alzheimer's disease locus.","volume":"269","author":"E Levy-Lahad","year":"1995","journal-title":"Science"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/376775a0","article-title":"Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene.","volume":"376","author":"EI Rogaev","year":"1995","journal-title":"Nature"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1212\/WNL.43.8.1467","article-title":"Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease.","volume":"43","author":"AM Saunders","year":"1993","journal-title":"Neurology"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1126\/science.8346443","article-title":"Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.","volume":"261","author":"EH Corder","year":"1993","journal-title":"Science"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1073\/pnas.90.5.1977","article-title":"Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.","volume":"90","author":"WJ Strittmatter","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"M117","DOI":"10.1093\/gerona\/52A.2.M117","article-title":"Heritability for Alzheimer's disease: the study of dementia in Swedish twins.","volume":"52","author":"M Gatz","year":"1997","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1001\/archneur.61.12.1930","article-title":"APOE genotype, family history of dementia, and Alzheimer disease risk: a 6-year follow-up study.","volume":"61","author":"W Huang","year":"2004","journal-title":"Arch Neurol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1093\/hmg\/ddm031","article-title":"Evidence for novel susceptibility genes for late-onset Alzheimer's disease from a genome-wide association study of putative functional variants.","volume":"16","author":"A Grupe","year":"2007","journal-title":"Hum Mol Genet"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"613","DOI":"10.4088\/JCP.v68n0419","article-title":"A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease.","volume":"68","author":"KD Coon","year":"2007","journal-title":"J Clin Psychiatry"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.neuron.2007.05.022","article-title":"GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers.","volume":"54","author":"EM Reiman","year":"2007","journal-title":"Neuron"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1755-8794-1-44","article-title":"A genome-wide association study for late-onset Alzheimer's disease using DNA pooling.","volume":"1","author":"R Abraham","year":"2008","journal-title":"BMC Med Genomics"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ajhg.2008.10.008","article-title":"Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE.","volume":"83","author":"L Bertram","year":"2008","journal-title":"Am J Hum Genet"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ajhg.2008.12.008","article-title":"Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease.","volume":"84","author":"GW Beecham","year":"2009","journal-title":"Am J Hum Genet"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/ng.305","article-title":"Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease.","volume":"41","author":"MM Carrasquillo","year":"2009","journal-title":"Nat Genet"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/ng.439","article-title":"Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease.","volume":"41","author":"JC Lambert","year":"2009","journal-title":"Nat Genet"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/ng.440","article-title":"Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease.","volume":"41","author":"D Harold","year":"2009","journal-title":"Nat Genet"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1001\/jama.2010.574","article-title":"Genome-wide analysis of genetic loci associated with Alzheimer disease.","volume":"303","author":"S Seshadri","year":"2010","journal-title":"Jama"},{"key":"ref23","first-page":"45","article-title":"Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease.","volume":"65","author":"H Li","year":"2008","journal-title":"Arch Neurol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1126\/science.1156409","article-title":"Genetic mapping in human disease.","volume":"322","author":"D Altshuler","year":"2008","journal-title":"Science"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature05911","article-title":"Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.","volume":"447","year":"2007","journal-title":"Nature"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"4612","DOI":"10.1074\/jbc.M109.079855","article-title":"Mitochondrial C1-Tetrahydrofolate Synthase (MTHFD1L) Supports the Flow of Mitochondrial One-carbon Units into the Methyl Cycle in Embryos.","volume":"285","author":"ST Pike","year":"2010","journal-title":"J Biol Chem"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.archger.2008.03.009","article-title":"Hyperhomocysteinemia and Alzheimer's disease: A systematic review.","volume":"48","author":"F Van Dam","year":"2009","journal-title":"Arch Gerontol Geriatr"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1474-4422(03)00438-1","article-title":"Homocysteine and Alzheimer's disease.","volume":"2","author":"MS Morris","year":"2003","journal-title":"Lancet Neurol"},{"key":"ref29","first-page":"471","article-title":"Hyperhomocysteinemia: a new risk factor for degenerative diseases.","volume":"48","author":"W Herrmann","year":"2002","journal-title":"Clin Lab"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0140-6736(00)03577-7","article-title":"Pathogenesis and genetics of pre-eclampsia.","volume":"357","author":"JM Roberts","year":"2001","journal-title":"Lancet"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jdiacomp.2003.12.003","article-title":"Total homocysteine levels relation with chronic complications of diabetes, body composition, and other cardiovascular risk factors in a population of patients with diabetes mellitus type 2.","volume":"19","author":"DA de Luis","year":"2005","journal-title":"J Diabetes Complications"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1093\/ije\/24.4.704","article-title":"Serum total homocysteine and coronary heart disease.","volume":"24","author":"E Arnesen","year":"1995","journal-title":"Int J Epidemiol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1056\/NEJMoa072366","article-title":"Genomewide association analysis of coronary artery disease.","volume":"357","author":"NJ Samani","year":"2007","journal-title":"N Engl J Med"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1001\/jama.1997.03540340047031","article-title":"Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.","volume":"277","author":"DA Snowdon","year":"1997","journal-title":"Jama"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/jnr.10416","article-title":"Multiple aspects of homocysteine neurotoxicity: glutamate excitotoxicity, kinase hyperactivation and DNA damage.","volume":"70","author":"PI Ho","year":"2002","journal-title":"J Neurosci Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1212\/WNL.58.9.1395","article-title":"Functional vitamin B(12) deficiency and Alzheimer disease.","volume":"58","author":"A McCaddon","year":"2002","journal-title":"Neurology"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/S0006-3223(02)01451-8","article-title":"Alzheimer's disease and total plasma aminothiols.","volume":"53","author":"A McCaddon","year":"2003","journal-title":"Biol Psychiatry"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0166-2236(03)00032-8","article-title":"Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders.","volume":"26","author":"MP Mattson","year":"2003","journal-title":"Trends Neurosci"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"e2750","DOI":"10.1371\/journal.pone.0002750","article-title":"iTRAQ analysis of complex proteome alterations in 3xTgAD Alzheimer's mice: understanding the interface between physiology and disease.","volume":"3","author":"B Martin","year":"2008","journal-title":"PLoS One"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e8593","DOI":"10.1371\/journal.pone.0008593","article-title":"Treatment of Alzheimer's disease with anti-homocysteic acid antibody in 3xTg-AD male mice.","volume":"5","author":"T Hasegawa","year":"2010","journal-title":"PLoS One"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1086\/341034","article-title":"A second locus for very-late-onset Alzheimer disease: a genome scan reveals linkage to 20p and epistasis between 20p and the amyloid precursor protein region.","volume":"71","author":"JM Olson","year":"2002","journal-title":"Am J Hum Genet"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/hmg\/ddg007","article-title":"Results of a high-resolution genome screen of 437 Alzheimer's disease families.","volume":"12","author":"D Blacker","year":"2003","journal-title":"Hum Mol Genet"},{"key":"ref43","article-title":"PCDH11X variation is not associated with late-onset Alzheimer disease susceptibility.","author":"GW Beecham","year":"2010","journal-title":"Psychiatr Genet"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"641","DOI":"10.2118\/2993-PA","article-title":"Competitive Bidding in High-Risk Situations.","volume":"23","author":"EC Capen","year":"1971","journal-title":"Journal of Petroleum Technology"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1001\/archneur.63.11.1591","article-title":"Expanded genomewide scan implicates a novel locus at 3q28 among Caribbean hispanics with familial Alzheimer disease.","volume":"63","author":"JH Lee","year":"2006","journal-title":"Arch Neurol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/ng.f.136","article-title":"Common and rare variants in multifactorial susceptibility to common diseases.","volume":"40","author":"W Bodmer","year":"2008","journal-title":"Nat Genet"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1001\/archneur.55.9.1185","article-title":"Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease.","volume":"55","author":"V Haroutunian","year":"1998","journal-title":"Arch Neurol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1469-1809.2009.00560.x","article-title":"Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease.","volume":"74","author":"TL Edwards","year":"2010","journal-title":"Ann Hum Genet"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1212\/WNL.34.7.939","article-title":"Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease.","volume":"34","author":"G McKhann","year":"1984","journal-title":"Neurology"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1212\/WNL.43.2.250","article-title":"Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.","volume":"43","author":"GC Roman","year":"1993","journal-title":"Neurology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1002\/ajmg.b.30298","article-title":"Lack of association between UBQLN1 and Alzheimer disease.","volume":"141B","author":"MA Slifer","year":"2006","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1093\/bioinformatics\/17.8.742","article-title":"GRR: graphical representation of relationship errors.","volume":"17","author":"GR Abecasis","year":"2001","journal-title":"Bioinformatics"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1093\/genetics\/155.2.945","article-title":"Inference of population structure using multilocus genotype data.","volume":"155","author":"JK Pritchard","year":"2000","journal-title":"Genetics"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1086\/302959","article-title":"Association mapping in structured populations.","volume":"67","author":"JK Pritchard","year":"2000","journal-title":"Am J Hum Genet"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/ng1847","article-title":"Principal components analysis corrects for stratification in genome-wide association studies.","volume":"38","author":"AL Price","year":"2006","journal-title":"Nat Genet"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses.","volume":"81","author":"S Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1038\/ng2088","article-title":"A new multipoint method for genome-wide association studies by imputation of genotypes.","volume":"39","author":"J Marchini","year":"2007","journal-title":"Nat Genet"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1002\/gepi.20472","article-title":"Genome-wide association studies: quality control and population-based measures.","volume":"33","author":"A Ziegler","year":"2009","journal-title":"Genet Epidemiol"},{"key":"ref59"},{"key":"ref60","first-page":"521","article-title":"Biological markers for therapeutic trials in Alzheimer's disease. Proceedings of the biological markers working group; NIA initiative on neuroimaging in Alzheimer's disease.","volume":"24","author":"RA Frank","year":"2003","journal-title":"Neurobiol Aging"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1212\/WNL.42.1.115","article-title":"Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study.","volume":"42","author":"DL Bachman","year":"1992","journal-title":"Neurology"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1093\/bioinformatics\/18.12.1681","article-title":"SNPper: retrieval and analysis of human SNPs.","volume":"18","author":"A Riva","year":"2002","journal-title":"Bioinformatics"}],"container-title":["PLoS Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pgen.1001130","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T14:38:52Z","timestamp":1636555132000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1001130"}},"subtitle":[],"editor":[{"given":"Joshua M.","family":"Akey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2010,9,23]]},"references-count":62,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2010,9,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1001130","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,23]]}}}