Jenkins Edmund C, Marchi Elaine J, Velinov Milen T, Ye Lingling, Krinsky-McHale Sharon J, Zigman Warren B, Schupf Nicole, Silverman Wayne P
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.
Am J Med Genet B Neuropsychiatr Genet. 2017 Dec;174(8):772-778. doi: 10.1002/ajmg.b.32575. Epub 2017 Aug 30.
Telomere shortening was shown to parallel Alzheimer's disease (AD) associated dementia. By using a dual PNA Probe system we have developed a practical method for comparing telomere length in T-lymphocyte interphases from individuals with Down syndrome (DS) with and without "mild cognitive impairment" (MCI-DS) and demonstrated that telomere length can serve as a valid biomarker for the onset of MCI-DS in this high-risk population. To verify progressive cognitive decline we have now examined sequential changes in telomere length in 10 adults with DS (N = 4 Female, N = 6 Male) developing MCI-DS. Cases were selected blind to telomere length from a sample of adults with DS previously enrolled in a prospective longitudinal study at 18-month intervals with clinical and telomere assessments: (1) MCI-DS group data were collected approximately three years prior to development of MCI-DS; (2) 18 months later; (3) when MCI-DS 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-DS (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-months prior to recognition of MCI-DS onset and completely non-overlapping distributions of telomere measures were observed by the time of MCI-DS 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.
端粒缩短与阿尔茨海默病（AD）相关痴呆症呈平行关系。通过使用双肽核酸（PNA）探针系统，我们开发了一种实用方法，用于比较唐氏综合征（DS）患者中有无“轻度认知障碍”（MCI-DS）的个体在T淋巴细胞间期的端粒长度，并证明端粒长度可作为该高危人群中MCI-DS发病的有效生物标志物。为了验证认知功能的进行性下降，我们现在检查了10名患有MCI-DS的唐氏综合征成年患者（4名女性，6名男性）端粒长度的连续变化。病例是从先前参加前瞻性纵向研究的唐氏综合征成年样本中，在不了解端粒长度的情况下挑选出来的，研究每隔18个月进行临床和端粒评估：（1）MCI-DS组的数据在MCI-DS发病前约三年收集；（2）18个月后；（3）首次观察到MCI-DS时。将这些端粒测量结果与另外10名年龄和性别匹配但无MCI-DS迹象的唐氏综合征成年患者（对照组）的测量结果进行比较。使用了用于端粒的PNA（肽核酸）探针以及2号染色体着丝粒探针。结果表明，病例组和对照组的端粒均随时间缩短。在识别MCI-DS发病前18个月出现了组间差异，到MCI-DS发病时观察到端粒测量值的分布完全不重叠。这项研究进一步积累了证据，证明端粒长度作为唐氏综合征成年患者AD进展的早期生物标志物具有重要价值。
