TY - JOUR
T1 - Telomere longitudinal shortening as a biomarker for dementia status of adults with Down syndrome
AU - Jenkins, Edmund C.
AU - Ye, Lingling
AU - Krinsky-Mchale, Sharon J.
AU - Zigman, Warren B.
AU - Schupf, Nicole
AU - Silverman, Wayne P.
N1 - Funding Information:
Thanks are due the research participants and various cooperating agencies as well as all staff involved in this project including Deborah Pang, Tracy Listwan, Cynthia Kovacs, Marcia Dabbene, Robert Ryan, Sheelagh Vietze. We also thank Dr.Ezzat El-Akkad of the Graphic Arts Department and Mr. Lawrence Black, Institute Librarian
Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Biomarker
KW - Dementia status
KW - Down syndrome
KW - FISH with PNA (peptide nucleic acid) probes
KW - Mild cognitive impairment (MCI)
KW - Telomere length in light intensity units
KW - Telomere length in microns
KW - Telomere longitudinal shortening
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U2 - 10.1002/ajmg.b.32389
DO - 10.1002/ajmg.b.32389
M3 - Article
C2 - 26593971
AN - SCOPUS:84958150628
SN - 1552-4841
VL - 171
SP - 169
EP - 174
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 2
ER -