Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Alzheimer's Disease Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Mov Disord. 2017 Dec;32(12):1764-1771. doi: 10.1002/mds.27196. Epub 2017 Oct 27.
Cognitive dysfunction is common in progressive supranuclear palsy, but the influence of genetics on cognition in this disorder has not been well studied. The objective of this study was to investigate the effect of genes previously identified as risk alleles, including microtubule-associated protein tau, myelin-associated oligodendrocyte basic protein, eukaryotic translation initiation factor 2-alpha kinase 3, and syntaxin 6, as well as apolipoprotein E, on cognitive function in progressive supranuclear palsy.
The sample was composed of 305 participants who met criteria for possible or probable progressive supranuclear palsy. Genetic information was determined by TaqMan genotyping assays. A neuropsychological battery was administered to all study participants. Measures included in the battery evaluated for general cognition, executive function, memory, attention, language, and visuospatial ability.
Cognition did not vary significantly between individuals homozygous or heterozygous for the microtubule-associated protein tau H1 haplotype. However, cognition varied significantly at the subhaplotype level, with carriers of the microtubule-associated protein tau rs242557/A allele, which marks the H1c subhaplotype, performing better than noncarriers on measures of general cognitive function, executive function, and attention. No associations were found for other genes.
The results of the current study indicate that variations in microtubule-associated protein tau influence cognition in progressive supranuclear palsy. Although the H1c-specific rs242557/A allele is a risk factor for progressive supranuclear palsy, carriers of this allele may exhibit better cognition than non-carriers in patients with the atypical parkinsonian syndrome. Further studies are needed. © 2017 International Parkinson and Movement Disorder Society.
认知功能障碍在进行性核上性麻痹中很常见，但遗传对这种疾病认知的影响尚未得到很好的研究。本研究的目的是研究以前确定的风险等位基因，包括微管相关蛋白 tau、髓鞘相关少突胶质细胞碱性蛋白、真核翻译起始因子 2-α 激酶 3 和突触素 6 以及载脂蛋白 E，对进行性核上性麻痹认知功能的影响。
该样本由 305 名符合可能或可能进行性核上性麻痹标准的参与者组成。通过 TaqMan 基因分型测定确定遗传信息。对所有研究参与者进行神经心理学测试。测试包括评估一般认知、执行功能、记忆、注意力、语言和视空间能力的测试。
微管相关蛋白 tau H1 单倍型纯合或杂合的个体之间的认知没有显著差异。然而，在亚单倍型水平上认知存在显著差异，携带微管相关蛋白 tau rs242557/A 等位基因的个体（标志着 H1c 亚单倍型）在一般认知功能、执行功能和注意力的测试中表现优于非携带者。其他基因没有发现相关性。
目前的研究结果表明，微管相关蛋白 tau 的变异影响进行性核上性麻痹的认知。虽然 H1c 特异性 rs242557/A 等位基因是进行性核上性麻痹的风险因素，但在非典型帕金森综合征患者中，携带该等位基因的个体的认知可能比非携带者更好。需要进一步研究。 © 2017 国际帕金森病和运动障碍学会。
