Collaborative Genomics Group, Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; Cooperative Research Centre for Mental Health, Carlton South, Victoria, Australia.
CSIRO Health and Biosecurity, Parkville, Victoria, Australia; Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
Neurobiol Aging. 2019 Apr;76:162-165. doi: 10.1016/j.neurobiolaging.2018.12.014. Epub 2019 Jan 6.
The longevity gene Klotho (KL), specifically the functional KL-VS variant, has previously been associated with cognition and rates of cognitive decline. This study aimed to determine whether KL-VS associations with cognition were observable in preclinical Alzheimer's disease (AD). The study also aimed to determine whether there was a combined influence of KL-VS, neocortical amyloid-β (Aβ) burden, and carriage of the apolipoprotein E (APOE) ε4 allele on cognitive decline. This study involved 581 Aβ-imaged, cognitively normal older adults, enrolled in the Australian Imaging, Biomarkers and Lifestyle Study of Aging. Linear mixed effects models revealed no significant associations between KL-VS and cognitive decline independently or in combination with Aβ burden and APOE ε4 genotype. Overall, previous associations reported between KL-VS and cognitive decline are not observed at the preclinical stages of AD. Furthermore, the results do not support the hypothesis that KL-VS has a modifying effect on Aβ burden and APOE ε4-driven cognitive decline in preclinical AD.
长寿基因 Klotho（KL），特别是功能性 KL-VS 变体，先前与认知功能和认知下降速度有关。本研究旨在确定 KL-VS 是否与临床前阿尔茨海默病（AD）的认知有关。该研究还旨在确定 KL-VS、新皮层淀粉样蛋白-β（Aβ）负担以及载脂蛋白 E（APOE）ε4 等位基因的共同影响是否对认知下降有影响。该研究涉及澳大利亚成像、生物标志物和衰老生活方式研究中的 581 名 Aβ 成像、认知正常的老年人。线性混合效应模型显示，KL-VS 与认知下降之间没有独立或与 Aβ 负担和 APOE ε4 基因型联合存在显著关联。总体而言，在 AD 的临床前阶段，先前报道的 KL-VS 与认知下降之间的关联并不明显。此外，结果不支持 KL-VS 对临床前 AD 中 Aβ 负担和 APOE ε4 驱动的认知下降具有修饰作用的假设。
