{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:59:43Z","timestamp":1773813583719,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T00:00:00Z","timestamp":1448236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01\u2010HD35897"],"award-info":[{"award-number":["P01\u2010HD35897"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010HD37425"],"award-info":[{"award-number":["R01\u2010HD37425"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010AG\u201014673"],"award-info":[{"award-number":["R01\u2010AG\u201014673"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30\u2010HD024061"],"award-info":[{"award-number":["P30\u2010HD024061"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:sec><jats:label\/><jats:p>Previous studies have suggested that Alzheimer's disease (AD) causes an accelerated shortening of telomeres, the ends of chromosomes consisting of highly conserved TTAGGG repeats that, because of unidirectional 5\u2032\u20133\u2032 DNA synthesis, lose end point material with each cell division. Our own previous work suggested that telomere length of T\u2010lymphocytes might be a remarkably accurate biomarker for \u201cmild cognitive impairment\u201d in adults with Down syndrome (MCI\u2010DS), a population at dramatically high risk for AD. To verify that the progression of cognitive and functional losses due to AD produced this observed telomere shortening, we have now examined sequential changes in telomere length in five individuals with Down syndrome (3F, 2M) as they transitioned from preclinical AD to MCI\u2010DS (N\u2009=\u20094) or dementia (N\u2009=\u20091). As in our previous studies, we used PNA (peptide nucleic acid) probes for telomeres and the chromosome 2 centromere (as an \u201cinternal standard\u201d expected to be unaffected by aging or dementia status), with samples from the same individuals now collected prior to and following development of MCI\u2010DS or dementia. Consistent shortening of telomere length was observed over time. Further comparisons with our previous cross\u2010sectional findings indicated that telomere lengths prior to clinical decline were similar to those of other adults with Down syndrome (DS) who have not experienced clinical decline while telomere lengths following transition to MCI\u2010DS or dementia in the current study were comparable to those of other adults with DS who have developed MCI\u2010DS or dementia. Taken together, findings indicate that telomere length has significant promise as a biomarker of clinical progression of AD for adults with DS, and further longitudinal studies of a larger sample of individuals with DS are clearly warranted to validate these findings and determine if and how factors affecting AD risk also influence these measures of telomere length. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.b.32389","type":"journal-article","created":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T11:45:26Z","timestamp":1448279126000},"page":"169-174","source":"Crossref","is-referenced-by-count":14,"title":["Telomere longitudinal shortening as a biomarker for dementia status of adults with Down syndrome"],"prefix":"10.1002","volume":"171","author":[{"given":"Edmund C.","family":"Jenkins","sequence":"first","affiliation":[{"name":"New York State Institute for Basic Research in Developmental Disabilities Staten Island New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Ye","sequence":"additional","affiliation":[{"name":"New York State Institute for Basic Research in Developmental Disabilities Staten Island New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon J.","family":"Krinsky\u2010McHale","sequence":"additional","affiliation":[{"name":"New York State Institute for Basic Research in Developmental Disabilities Staten Island New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Warren B.","family":"Zigman","sequence":"additional","affiliation":[{"name":"New York State Institute for Basic Research in Developmental Disabilities Staten Island New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Schupf","sequence":"additional","affiliation":[{"name":"New York State Institute for Basic Research in Developmental Disabilities Staten Island New York"},{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wayne P.","family":"Silverman","sequence":"additional","affiliation":[{"name":"The Kennedy Krieger Institute and The Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,11,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10114"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-012-8207-9"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407162101"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/109454503323028894"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1192\/bjp.22.98.169","article-title":"Kalmuc idiocy: Report of a case with autopsy with notes on sixty\u2010two cases","volume":"22","author":"Fraser J","year":"1876","journal-title":"J Ment Sci"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3810169"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2014.2746"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403924200"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g4227"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2012.1541"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12325"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.05.021"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.05.098"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.06.001"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cryobiol.2012.03.005"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32066"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.105.2.102"},{"issue":"9","key":"e_1_2_6_20_1","doi-asserted-by":"crossref","DOI":"10.5070\/D3209023917","article-title":"Dyskeratosis congenita","volume":"20","author":"Keeling B","year":"2014","journal-title":"Dermatol Online J"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddrr.1126"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.5.685"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1997.6777"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.15.3164"},{"key":"e_1_2_6_25_1","first-page":"67","volume-title":"Aging and the Brain","author":"Malamud N","year":"1972"},{"issue":"3","key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.2310\/JIM.0b013e3182814cc2","article-title":"Telomere length and cardiorespiratory fitness in marathon runners","volume":"61","author":"Mathur S","year":"2013","journal-title":"J Investig Med"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/NNR.0000000000000037"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2011.12.005"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-5193(73)90198-7"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00043-X"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20271"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.06.013"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.70"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198906013202203"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1352\/0895-8017(2004)109<111:DIAWMR>2.0.CO;2"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/jppi.12042"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/NNR.0000000000000009"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2890207"},{"key":"e_1_2_6_39_1","first-page":"197","article-title":"Origin of concataeric T4 DNA","volume":"239","author":"Watson JD","year":"1972","journal-title":"Nat Biol"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318202bfa1"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2014.03.019"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410170310"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1352\/0895-8017(2002)107<0161:IATPOA>2.0.CO;2"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddrr.1128"}],"container-title":["American Journal of Medical Genetics Part B: Neuropsychiatric Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.b.32389","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.b.32389","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T06:23:47Z","timestamp":1695709427000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.b.32389"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,23]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1002\/ajmg.b.32389"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.b.32389","archive":["Portico"],"relation":{},"ISSN":["1552-4841","1552-485X"],"issn-type":[{"value":"1552-4841","type":"print"},{"value":"1552-485X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,23]]}}}