Panossian L A, Porter V R, Valenzuela H F, Zhu X, Reback Erin, Masterman D, Cummings J L, Effros R B
Department of Pathology, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Neurobiol Aging. 2003 Jan-Feb;24(1):77-84. doi: 10.1016/s0197-4580(02)00043-x.
Telomeres, the repeated sequences that cap chromosome ends, undergo shortening with each cell division, and therefore serve as markers of a cell's replicative history. In vivo, clonal expansion of T cells during immune responses to both foreign and autoantigens is associated with telomere shortening. To investigate possible immune alterations in Alzheimer's disease (AD) that might impact current vaccine-based therapeutic strategies, we analyzed telomere lengths in immune cell populations from AD patients. Our data show a significant telomere shortening in PBMC from AD versus controls (P=0.04). Importantly, telomere length of T cells, but not of B cells or monocytes, correlated with AD disease status, measured by Mini Mental Status Exam (MMSE) scores (P=0.025). T cell telomere length also inversely correlated with serum levels of the proinflammatory cytokine TNFalpha (a clinical marker of disease status), with the proportion of CD8+ T cells lacking expression of the CD28 costimulatory molecule, and with apoptosis. These findings suggest an immune involvement in AD pathogenesis.
端粒是位于染色体末端的重复序列，随着细胞每次分裂而缩短，因此可作为细胞复制历史的标志物。在体内，T细胞在对外源抗原和自身抗原的免疫反应过程中的克隆扩增与端粒缩短有关。为了研究阿尔茨海默病（AD）中可能影响当前基于疫苗的治疗策略的免疫改变，我们分析了AD患者免疫细胞群体中的端粒长度。我们的数据显示，与对照组相比，AD患者外周血单核细胞（PBMC）中的端粒显著缩短（P = 0.04）。重要的是，通过简易精神状态检查表（MMSE）评分测量，T细胞而非B细胞或单核细胞的端粒长度与AD疾病状态相关（P = 0.025）。T细胞端粒长度还与促炎细胞因子肿瘤坏死因子α（TNFα）的血清水平（疾病状态的临床标志物）、缺乏CD28共刺激分子表达的CD8 + T细胞比例以及细胞凋亡呈负相关。这些发现表明免疫参与了AD的发病机制。
