Increased ȁc;absence” of telomeres may indicate Alzheimer's disease/dementia status in older individuals with Down syndrome
- 作者：Edmund C. Jenkins ; Lingling Ye ; Hong Gu ; Samantha A. Ni ; Charlotte J. Duncan ; Milen Velinov ; Deborah Pang ; Sharon J. Krinsky-McHale ; Warren B. Zigman ; Nicole Schupf ; Wayne P. Silverman
- 关键词：Telomere number ; Down syndrome ; Alzheimer's disease ; Mild cognitive impairment
- 刊名：Neuroscience Letters
- 出版年：2008
- 期刊代码：52_03043940
- 类别：neu
- 出版时间：8 August 2008
- 卷：440
- 期：3
- 页码：340-343
- 文件大小：862 K
摘要
We have reported previously that telomeres (ends of chromosomes consisting of highly conserved TTAGGG repeats) were shorter in metaphase and interphase preparations in T lymphocytes from short-term whole blood cultures of women with Down syndrome (DS) and dementia compared to age-matched women with DS but without dementia [E.C. Jenkins, M.T. Velinov, L. Ye, H. Gu, S. Li, E.C. Jenkins Jr., S.S. Brooks, D. Pang, D.A. Devenny, W.B. Zigman, N. Schupf, W.P. Silverman, Telomere shortening in T lymphocytes of older individuals with Down syndrome and dementia, Neurobiol. Aging 27 (2006) 41–45]. Our previous study was carried out by measuring changes in fluorescence intensity [using an FITC-labeled peptide nucleic acid (PNA) probe (Applied Biosystems; DAKO) and Applied Imaging software], and we now report on a substantially simpler metric, counts of signals at the ends of chromosomes. Nine adults with DS and dementia plus four who are exhibiting declines in cognition analogous to mild cognitive impairment in the general population (MCI-DS) were compared to their pair-matched peers with DS but without dementia or MCI-DS. Results indicated that the number of chromosome ends that failed to exhibit fluorescent signal from the PNA telomere probe was higher for people with dementia or mild cognitive impairment (MCI-DS). Thus, a simple count of chromosome ends for the ȁc;presence/absence” of fluorescence may provide a valid biomarker of dementia status. If this is the case, then after additional research for validation to assure high specificity and sensitivity, the test may be used to identify and ultimately guide treatment for people at increased risk for developing mild cognitive impairment and/or dementia.