Laboratory of Functional Neuroscience, Pablo de Olavide University, Seville, Spain.
CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, Spain.
Cereb Cortex. 2019 Sep 13;29(10):4426-4437. doi: 10.1093/cercor/bhy323.
Evidence has shown that microRNAs (miRNAs) are involved in molecular pathways responsible for aging and prevalent aging-related chronic diseases. However, the lack of research linking circulating levels of miRNAs to changes in the aging brain hampers clinical translation. Here, we have investigated if serum expression of brain-enriched miRNAs that have been proposed as potential biomarkers in Alzheimer's disease (AD) (miR-9, miR-29b, miR-34a, miR-125b, and miR-146a) are also associated with cognitive functioning and changes of the cerebral cortex in normal elderly subjects. Results revealed that candidate miRNAs were linked to changes in cortical thickness (miR-9, miR-29b, miR-34a, and miR-125b), cortical glucose metabolism (miR-29b, miR-125b, and miR-146a), and cognitive performance (miR-9, miR-34a, and miR-125b). While both miR-29b and miR-125b were related to aging-related structural and metabolic cortical changes, only expression levels of miR-125b were associated with patterns of glucose consumption shown by cortical regions that correlated with executive function. Together, these findings suggest that serum expression of AD-related miRNAs are biologically meaningful in aging and may play a role as biomarkers of cerebral vulnerability in late life.
证据表明,microRNAs(miRNAs)参与了负责衰老和普遍的与衰老相关的慢性疾病的分子途径。然而,将循环 miRNA 水平与衰老大脑的变化联系起来的研究缺乏,这阻碍了临床转化。在这里,我们研究了在正常老年人中,是否脑内富含 miRNA 的血清表达与认知功能和大脑皮层的变化有关,这些 miRNA 已被提出作为阿尔茨海默病(AD)的潜在生物标志物(miR-9、miR-29b、miR-34a、miR-125b 和 miR-146a)。结果表明,候选 miRNA 与皮质厚度变化(miR-9、miR-29b、miR-34a 和 miR-125b)、皮质葡萄糖代谢(miR-29b、miR-125b 和 miR-146a)和认知表现(miR-9、miR-34a 和 miR-125b)有关。虽然 miR-29b 和 miR-125b 都与衰老相关的结构和代谢性皮质变化有关,但只有 miR-125b 的表达水平与与执行功能相关的皮质区域的葡萄糖消耗模式相关。总之,这些发现表明,AD 相关 miRNA 的血清表达在衰老中具有生物学意义,并且可能作为晚年大脑脆弱性的生物标志物发挥作用。