Telomere length shortening in patients with dementia with Lewy bodies
Telomere length shortening in patients with dementia with Lewy bodies
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DOI：
10.1111/j.1468-1331.2011.03655.x
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发表时间：
2012-06-01
影响因子：
5.1
通讯作者：
Iwamoto, T.
中科院分区：
文献类型：
--
作者：
Kume, K.;Kikukawa, M.;Iwamoto, T.
背景和目的：端粒长度缩短被认为与多种年龄相关的疾病有关，特别是在阿尔茨海默病和血管性痴呆等痴呆症中。然而，路易体痴呆(DLB)患者端粒长度的变化仍不清楚。为了阐明这些变化，我们开始测定外周血白细胞的端粒长度以及尿中8-羟基脱氧鸟苷(8-OHdG)的水平作为DLB氧化应激的标志。方法：采集33例临床诊断为DLB的患者和35例年龄匹配的非痴呆老年对照(NEC)的血样。用实时定量聚合酶链式反应测定白细胞基因组DNA的端粒长度，用高效液相色谱法测定尿液8-OHdG水平来评价氧化应激状态。结果：DLB组的端粒长度明显短于NEC组。DLB组尿8-OHdG水平显著高于NEC组。在DLB组中，端粒长度与年龄呈负相关；然而，端粒长度与包括病程、认知功能下降的严重程度、认知功能是否有波动、视觉幻觉和帕金森病等临床表现没有显著关系。在两组患者中，端粒长度与尿8-OHdG水平的相关性均不显著。结论：这些发现表明DLB的发病机制被认为是一个加速衰老的过程。
Background and purpose: Shortened telomere length has been considered to be associated with various age-related diseases, especially in dementia such as Alzheimers disease and vascular dementia. However, changes in telomere length in dementia with Lewy bodies (DLB) remain unclear. To elucidate these changes, we set out to determine telomere length in peripheral leukocytes as well as the level of urinary 8-hydroxy-deoxyguanosine (8-OHdG) as a marker of oxidative stress in DLB. Methods: Blood samples were obtained from 33 patients with a clinical diagnosis of probable DLB and 35 age-matched, non-demented elderly controls (NEC). Telomere length was assessed by quantitative real-time polymerase chain reaction of genomic DNA extracted from leukocytes, whereas oxidative stress was assessed on the basis of urine 8-OHdG level, which was measured using high-performance liquid chromatography. Results: Telomere length was significantly shorter in the DLB group than in the NEC group. Urinary 8-OHdG levels were significantly higher in the DLB group than in the NEC group. There was a negative correlation between telomere length and age in the DLB group; however, there were no significant relationships between telomere length and clinical findings including disease duration, severity of cognitive decline, presence or absence of fluctuation in cognitive function, visual hallucinations, and Parkinsonism. In both groups, the correlation between telomere length and urinary 8-OHdG levels was not significant. Conclusions: These findings indicate that the etiopathology of DLB is considered to be an accelerated aging process.