Telomere length and brain imaging phenotypes in UK Biobank.

Telomere length and brain imaging phenotypes in UK Biobank.
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DOI:
10.1371/journal.pone.0282363
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发表时间:
2023
期刊:
影响因子:
3.7
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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端粒在染色体末端形成保护帽,它们的磨损是生物衰老的标志。短端粒与神经和精神疾病(包括痴呆症)的风险增加有关。这种风险的潜在机制尚不清楚,可能涉及大脑结构和功能。然而,端粒长度和神经影像学标记物之间的关系是很差的特点。在这里,我们发现白细胞端粒长度(LTL)与31,661名英国生物样本库参与者的多模态MRI表型相关。较长的LTL与以下因素有关:i)包括海马在内的较大的整体和皮质下灰质体积,ii)感觉皮质中较低的T1加权灰白色组织对比度,iii)胼胝体和联合纤维中的白质微结构测量,iv)较低的白色物质高信号体积,以及v)较低的基底神经节铁。更长的LTL对某些相关的临床表现具有保护作用,即全因痴呆(HR 0.93,95%CI:0.91-0.96),但对中风或帕金森病没有保护作用。LTL与神经退行性疾病的多种MRI内表型相关,这表明较长的LTL可能提供对痴呆的保护的途径。
Telomeres form protective caps at the ends of chromosomes, and their attrition is a marker of biological aging. Short telomeres are associated with an increased risk of neurological and psychiatric disorders including dementia. The mechanism underlying this risk is unclear, and may involve brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized. Here we show that leucocyte telomere length (LTL) is associated with multi-modal MRI phenotypes in 31,661 UK Biobank participants. Longer LTL is associated with: i) larger global and subcortical grey matter volumes including the hippocampus, ii) lower T1-weighted grey-white tissue contrast in sensory cortices, iii) white-matter microstructure measures in corpus callosum and association fibres, iv) lower volume of white matter hyperintensities, and v) lower basal ganglia iron. Longer LTL was protective against certain related clinical manifestations, namely all-cause dementia (HR 0.93, 95% CI: 0.91–0.96), but not stroke or Parkinson’s disease. LTL is associated with multiple MRI endophenotypes of neurodegenerative disease, suggesting a pathway by which longer LTL may confer protective against dementia.
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