title: Telomere longitudinal shortening as a biomarker for dementia status of adults with Down syndrome.
abstract: 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'-3' DNA synthesis, lose end point material with each cell division. Our own previous work suggested that telomere length of T-lymphocytes might be a remarkably accurate biomarker for "mild cognitive impairment" in adults with Down syndrome (MCI-DS), 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-DS (N = 4) or dementia (N = 1). As in our previous studies, we used PNA (peptide nucleic acid) probes for telomeres and the chromosome 2 centromere (as an "internal standard" expected to be unaffected by aging or dementia status), with samples from the same individuals now collected prior to and following development of MCI-DS or dementia. Consistent shortening of telomere length was observed over time. Further comparisons with our previous cross-sectional 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-DS or dementia in the current study were comparable to those of other adults with DS who have developed MCI-DS 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.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
authors.forename: Edmund C
authors.initials: EC
authors.lastname: Jenkins
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
authors.forename: Lingling
authors.initials: L
authors.lastname: Ye
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Krinsky-McHale
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York.
authors.forename: Warren B
authors.initials: WB
authors.lastname: Zigman
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupf
authors.affiliation: The Kennedy Krieger Institute and The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Wayne P
authors.initials: WP
authors.lastname: Silverman
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D003704:Dementia / Q000150:complications* / Q000235:genetics*; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008677:Metaphase / Q000235:genetics; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism; D059506:Telomere Shortening / Q000235:genetics*
chemical_list: D015415:Biomarkers
keywords: Down syndrome; FISH with PNA (peptide nucleic acid) probes; biomarker; dementia status; mild cognitive impairment (MCI); telomere length in light intensity units; telomere length in microns; telomere longitudinal shortening