title: Mild cognitive impairment identified in older individuals with Down syndrome by reduced telomere signal numbers and shorter telomeres measured in microns.
abstract: Previously, we established that short-term T lymphocyte cultures from people with Down syndrome (DS) and dementia (Alzheimer's disease) had shorter telomeres than did those from age- and sex-matched people with DS only, quantified as significantly reduced numbers of signals of peptide nucleic acid (PNA) telomere probes in whole metaphases [Jenkins et al. (2008); Neurosci Lett 440:340-343] as well as reduced telomere probe light intensity values in interphases [Jenkins et al. (2010); Neurobiol Aging 31:765-771]. We now describe shorter telomere length in adults with DS and mild cognitive impairment (MCI) compared to age- and sex-matched individuals with DS without MCI. Telomere length is quantified by reduced telomere signal numbers and shorter chromosome 1 telomeres measured in micrometers (microns). These findings were in agreement with quantitative light intensity measurements of chromosome 1 and chromosome 21 PNA telomere probes with and without the use of a "normalizing ratio" involving the fluorescence exhibited by a PNA probe for centromere 2, and with the use of light intensity measurements of interphase preparations. Most importantly, the distributions of chromosome 1 telomere lengths (in microns) were completely non-overlapping for adults with and without MCI, indicating that this measure has great promise as a biomarker for MCI as well as dementia in this population.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA. edjenkins.jenkins85@gmail.com
authors.forename: Edmund C
authors.initials: EC
authors.lastname: Jenkins
authors.forename: Lingling
authors.initials: L
authors.lastname: Ye
authors.forename: Milen
authors.initials: M
authors.lastname: Velinov
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Krinsky-McHale
authors.forename: Warren B
authors.initials: WB
authors.lastname: Zigman
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupf
authors.forename: Wayne P
authors.initials: WP
authors.lastname: Silverman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002503:Centromere / Q000378:metabolism; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D060825:Cognitive Dysfunction / Q000150:complications* / Q000235:genetics*; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics*; D005260:Female; D006801:Humans; D007399:Interphase; D008027:Light; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D020135:Peptide Nucleic Acids / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D059506:Telomere Shortening / Q000235:genetics*
chemical_list: D020135:Peptide Nucleic Acids