{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T07:15:22Z","timestamp":1780557322740,"version":"3.54.1"},"reference-count":46,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurobiology of Aging"],"published-print":{"date-parts":[[2014,4]]},"DOI":"10.1016\/j.neurobiolaging.2013.09.025","type":"journal-article","created":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T17:31:07Z","timestamp":1382981467000},"page":"936.e5-936.e12","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":44,"title":["Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population"],"prefix":"10.1016","volume":"35","author":[{"given":"Ardeshir","family":"Omoumi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Fok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talitha","family":"Greenwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Dessa","family":"Sadovnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard H.","family":"Feldman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ging-Yuek R.","family":"Hsiung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib1","series-title":"Diagnostic and Statistical Manual of Mental Disorders: DSM-III-R","author":"American Psychiatric Association","year":"1987"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/gm34","article-title":"Genetics of Alzheimer's disease: recent advances","volume":"1","author":"Avramopoulos","year":"2009","journal-title":"Genome Med."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib3","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/ajmg.b.30993","article-title":"APOE mRNA and protein expression in postmortem brain are modulated by an extended haplotype structure","volume":"153B","author":"Bekris","year":"2011","journal-title":"Am. J. Med. Genet. B Neuropsychiatry Genet."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib4","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/jhg.2011.123","article-title":"Functional analysis of APOE locus genetic variation implicates regional enhancers in the regulation of both TOMM40 and APOE","volume":"57","author":"Bekris","year":"2012","journal-title":"J.\u00a0Hum. Genet."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib5","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":"Bertram","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib6","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1001\/archneurol.2010.108","article-title":"Genetic variation and neuroimaging measures in Alzheimer disease","volume":"67","author":"Biffi","year":"2010","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib7","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/mp.2011.24","article-title":"Alzheimer risk associated with a copy number variation in the complement receptor 1 increasing C3b\/C4b binding sites","volume":"17","author":"Brouwers","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib8","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1001\/archneurol.2010.147","article-title":"Replication of CLU, CR1, and PICALM associations with Alzheimer disease","volume":"67","author":"Carrasquillo","year":"2010","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib9","doi-asserted-by":"crossref","first-page":"210.e1","DOI":"10.1016\/j.neurobiolaging.2011.09.016","article-title":"Polymorphisms of CR1, CLU and PICALM confer susceptibility of Alzheimer's disease in a southern Chinese population","volume":"33","author":"Chen","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib10","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0166-2236(00)01930-5","article-title":"The dephosphins: dephosphorylation by calcineurin triggers synaptic vesicle endocytosis","volume":"24","author":"Cousin","year":"2001","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib11","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nri2056","article-title":"Siglecs and their roles in the immune system","volume":"7","author":"Crocker","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib12","first-page":"899","article-title":"Canadian Study of Health and Aging: study methods and prevalence of dementia","volume":"150","author":"CSHA","year":"1994","journal-title":"CMAJ"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib13","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1212\/WNL.55.1.66","article-title":"The incidence of dementia in Canada: the Canadian Study of Health and Aging working group","volume":"55","author":"CSHA","year":"2000","journal-title":"Neurology"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib14","doi-asserted-by":"crossref","first-page":"9057","DOI":"10.1523\/JNEUROSCI.1469-06.2006","article-title":"Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction","volume":"26","author":"Devi","year":"2006","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib15","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1212\/WNL.44.9.1593","article-title":"Prevalence and types of dementia in the very old: results from the Canadian Study of Health and Aging","volume":"44","author":"Ebly","year":"1994","journal-title":"Neurology"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib16","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.1002\/pmic.200900015","article-title":"2-D DIGE analysis implicates cytoskeletal abnormalities in psychiatric disease","volume":"9","author":"English","year":"2009","journal-title":"Proteomics"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib17","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","article-title":"Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis: APOE and Alzheimer Disease Meta Analysis Consortium","volume":"278","author":"Farrer","year":"1997","journal-title":"JAMA"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib18","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1159\/000071189","article-title":"A\u00a0Canadian Cohort Study of Cognitive Impairment and Related Dementias (ACCORD): study methods and baseline results","volume":"22","author":"Feldman","year":"2003","journal-title":"Neuroepidemiology"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib19","first-page":"S10","article-title":"Incidence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts: neurologic diseases in the elderly research group","volume":"54","author":"Fratiglioni","year":"2000","journal-title":"Neurology"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib20","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1159\/000109914","article-title":"Standardization of the diagnosis of dementia in the Canadian Study of Health and Aging","volume":"15","author":"Graham","year":"1996","journal-title":"Neuroepidemiology"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib21","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":"Harold","year":"2009","journal-title":"Nat. Genet."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib22","article-title":"Genetic association of CR1 with Alzheimer's disease: a tentative disease mechanism","volume":"33","author":"Hazrati","year":"2012","journal-title":"Neurobiology, Neurobiol. Aging"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib23","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/ng.803","article-title":"Common variants at ABCA7, MS4A6A\/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease","volume":"43","author":"Hollingworth","year":"2011","journal-title":"Nat. Genet."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib24","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1503\/cmaj.1031789","article-title":"Apolipoprotein E epsilon4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging","volume":"171","author":"Hsiung","year":"2004","journal-title":"CMAJ"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib25","doi-asserted-by":"crossref","first-page":"e16616","DOI":"10.1371\/journal.pone.0016616","article-title":"Meta-analysis for genome-wide association study identifies multiple variants at the BIN1 locus associated with late-onset Alzheimer's disease","volume":"6","author":"Hu","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib26","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1001\/archneurol.2010.201","article-title":"Meta-analysis confirms CR1, CLU, and PICALM as Alzheimer disease risk loci and reveals interactions with APOE genotypes","volume":"67","author":"Jun","year":"2010","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib26a","doi-asserted-by":"crossref","first-page":"S496","DOI":"10.1016\/j.jalz.2011.05.2389","article-title":"A Canadidate causal variant in the CR1 locus","volume":"7","author":"Keenan","year":"2011","journal-title":"Alzheimer's & Demen."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1212\/WNL.0b013e318204a397","article-title":"Genome-wide association study of CSF biomarkers Abeta1-42, t-tau, and p-tau181p in the ADNI cohort","volume":"76","author":"Kim","year":"2011","journal-title":"Neurology"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib28","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/alzrt71","article-title":"CLU, CR1 and PICALM genes associate with Alzheimer's-related senile plaques","volume":"3","author":"Kok","year":"2011","journal-title":"Alzheimers Res. Ther."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib29","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":"Lambert","year":"2009","journal-title":"Nat. Genet."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib30","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1001\/archneurol.2010.292","article-title":"Identification of novel loci for Alzheimer disease and replication of CLU, PICALM, and BIN1 in Caribbean Hispanic individuals","volume":"68","author":"Lee","year":"2011","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib31","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1001\/archneurol.2007.3","article-title":"Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease","volume":"65","author":"Li","year":"2008","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib32","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":"McKhann","year":"1984","journal-title":"Neurology"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib33","doi-asserted-by":"crossref","first-page":"e1001130","DOI":"10.1371\/journal.pgen.1001130","article-title":"Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities","volume":"6","author":"Naj","year":"2010","journal-title":"PLoS Genet."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib34","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/ng.801","article-title":"Common variants at MS4A4\/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease","volume":"43","author":"Naj","year":"2011","journal-title":"Nat. Genet."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib35","doi-asserted-by":"crossref","first-page":"e6501","DOI":"10.1371\/journal.pone.0006501","article-title":"Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer's disease","volume":"4","author":"Potkin","year":"2009","journal-title":"PLoS One"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib36","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/j.neurobiolaging.2005.09.043","article-title":"Peripheral clearance of amyloid beta peptide by complement C3-dependent adherence to erythrocytes","volume":"27","author":"Rogers","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib37","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1001\/archneurol.2010.88","article-title":"An inherited variable poly-T repeat genotype in TOMM40 in Alzheimer disease","volume":"67","author":"Roses","year":"2010","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib38","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/S1474-4422(07)70291-0","article-title":"Lifetime risk of stroke and dementia: current concepts, and estimates from the Framingham Study","volume":"6","author":"Seshadri","year":"2007","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib40","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":"Strittmatter","year":"1993","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib41","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.ygeno.2009.01.003","article-title":"Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese","volume":"93","author":"Takei","year":"2009","journal-title":"Genomics"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib42","doi-asserted-by":"crossref","first-page":"e1001308","DOI":"10.1371\/journal.pgen.1001308","article-title":"Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE","volume":"7","author":"Wijsman","year":"2011","journal-title":"PLoS Genet."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib43","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1017\/S0317167100013949","article-title":"Early-onset familial Alzheimer's disease (EOFAD)","volume":"39","author":"Wu","year":"2012","journal-title":"Can. J. Neurol. Sci."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib44","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.neuroscience.2008.04.012","article-title":"Comparative proteomic analysis of brains of naturally aging mice","volume":"154","author":"Yang","year":"2008","journal-title":"Neuroscience"},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib45","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.cca.2010.06.013","article-title":"Implication of CLU gene polymorphisms in Chinese patients with Alzheimer's disease","volume":"411","author":"Yu","year":"2010","journal-title":"Clin. Chim. Acta."},{"key":"10.1016\/j.neurobiolaging.2013.09.025_bib46","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.ygeno.2007.02.002","article-title":"Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease: patterns of linkage disequilibrium and disease\/marker association","volume":"89","author":"Yu","year":"2007","journal-title":"Genomics"}],"container-title":["Neurobiology of Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0197458013004272?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0197458013004272?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T11:24:06Z","timestamp":1759317846000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0197458013004272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,4]]}},"alternative-id":["S0197458013004272"],"URL":"https:\/\/doi.org\/10.1016\/j.neurobiolaging.2013.09.025","relation":{},"ISSN":["0197-4580"],"issn-type":[{"value":"0197-4580","type":"print"}],"subject":[],"published":{"date-parts":[[2014,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population","name":"articletitle","label":"Article Title"},{"value":"Neurobiology of Aging","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neurobiolaging.2013.09.025","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}