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By using a dual PNA Probe system we have developed a practical method for comparing telomere length in T\u2010lymphocyte interphases from individuals with Down syndrome (DS) with and without \u201cmild cognitive impairment\u201d (MCI\u2010DS) and demonstrated that telomere length can serve as a valid biomarker for the onset of MCI\u2010DS in this high\u2010risk population. To verify progressive cognitive decline we have now examined sequential changes in telomere length in 10 adults with DS (<jats:italic>N<\/jats:italic>\u2009=\u20094 Female, <jats:italic>N<\/jats:italic>\u2009=\u20096 Male) developing MCI\u2010DS. Cases were selected blind to telomere length from a sample of adults with DS previously enrolled in a prospective longitudinal study at 18\u2010month intervals with clinical and telomere assessments: (1) MCI\u2010DS group data were collected approximately three years prior to development of MCI\u2010DS; (2) 18 months later; (3) when MCI\u2010DS was first observed. These telomere measures were compared to those from another 10 adults with DS matched by sex and approximate age but without indications of MCI\u2010DS (Controls). PNA (peptide nucleic acid) probes for telomeres together with a chromosome two centromere probe were used. Findings indicated telomere shortening over time for both Cases and Controls. Group differences emerged by 18\u2010months prior to recognition of MCI\u2010DS onset and completely non\u2010overlapping distributions of telomere measures were observed by the time of MCI\u2010DS onset. This study adds to accumulating evidence of the value of telomere length, as an early biomarker of AD progression in adults with Down syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.b.32575","type":"journal-article","created":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T11:28:27Z","timestamp":1504178907000},"page":"772-778","source":"Crossref","is-referenced-by-count":15,"title":["Longitudinal telomere shortening and early Alzheimer's disease progression in adults with down syndrome"],"prefix":"10.1002","volume":"174","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1982-7465","authenticated-orcid":false,"given":"Edmund C.","family":"Jenkins","sequence":"first","affiliation":[{"name":"New York State Institute for Basic Research in Developmental Disabilities Staten Island New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine J.","family":"Marchi","sequence":"additional","affiliation":[{"name":"New York State Institute for Basic Research in 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