Brain microRNAs are associated with variation in cognitive trajectory in advanced age.
Brain microRNAs are associated with variation in cognitive trajectory in advanced age.
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DOI：
10.1038/s41398-022-01806-3
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发表时间：
2022-02-01
影响因子：
6.8
通讯作者：
Wingo TS
中科院分区：
文献类型：
--
作者：
Wingo AP;Wang M;Liu J;Breen MS;Yang HS;Tang B;Schneider JA;Seyfried NT;Lah JJ;Levey AI;Bennett DA;Jin P;De Jager PL;Wingo TS
随着年龄的增长，一些人随着时间的推移保持稳定的认知能力，而另一些人则会经历快速下降。这种认知轨迹的变化只能部分解释为常见的神经退行性病变。因此，我们的目的是确定新的分子过程中的认知轨迹的变化，使用脑microRNA谱，然后与脑转录组和蛋白质组的综合分析。个体认知轨迹来自四个纵向队列的老年脑捐赠者的纵向认知测试评分。死后大脑microRNA谱，转录组和蛋白质组来自背外侧前额叶皮层。认知轨迹的全球microRNA关联研究在发现队列（n = 454）和复制队列（n = 134）中进行，随后进行荟萃分析，鉴定出6种microRNA。其中，miR-132- 3 p和miR-29 a-3 p与认知轨迹最显著相关。它们分别解释了认知轨迹方差的18.2%和2.0%，并且独立于八种测量的神经退行性病变起作用。此外，整合转录组学和蛋白质组学分析显示，miR-132- 3 p与转录组共表达基因的47个模块中的24个显著相关，miR-29 a-3 p与3个模块显著相关，并在认知轨迹中分别鉴定了84个和214个miR-132- 3 p和miR-29 a-3 p的下游靶标。这是我们所知的第一个全球认知轨迹microRNA研究。我们鉴定了miR-29 a-3 p和miR-132- 3 p作为独立于八种已知脑病理的认知轨迹的新的和稳健的贡献者。我们的研究结果为未来研究机制和开发干预措施以提高老年人的认知稳定性奠定了基础。
In advancing age, some individuals maintain a stable cognitive performance over time, while others experience a rapid decline. Such variation in cognitive trajectory is only partially explained by common neurodegenerative pathologies. Hence, we aimed to identify new molecular processes underlying variation in cognitive trajectory using brain microRNA profile followed by an integrative analysis with brain transcriptome and proteome. Individual cognitive trajectories were derived from longitudinally assessed cognitive-test scores of older-adult brain donors from four longitudinal cohorts. Postmortem brain microRNA profiles, transcriptomes, and proteomes were derived from the dorsolateral prefrontal cortex. The global microRNA association study of cognitive trajectory was performed in a discovery (n = 454) and replication cohort (n = 134), followed by a meta-analysis that identified 6 microRNAs. Among these, miR-132-3p and miR-29a-3p were most significantly associated with cognitive trajectory. They explain 18.2% and 2.0% of the variance of cognitive trajectory, respectively, and act independently of the eight measured neurodegenerative pathologies. Furthermore, integrative transcriptomic and proteomic analyses revealed that miR-132-3p was significantly associated with 24 of the 47 modules of co-expressed genes of the transcriptome, miR-29a-3p with 3 modules, and identified 84 and 214 downstream targets of miR-132-3p and miR-29a-3p, respectively, in cognitive trajectory. This is the first global microRNA study of cognitive trajectory to our knowledge. We identified miR-29a-3p and miR-132-3p as novel and robust contributors to cognitive trajectory independently of the eight known cerebral pathologies. Our findings lay a foundation for future studies investigating mechanisms and developing interventions to enhance cognitive stability in advanced age.
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影响因子：
11.2
作者：
Boyle PA;Yu L;Wilson RS;Leurgans SE;Schneider JA;Bennett DA
通讯作者：
Bennett DA
DOI：
10.3233/jad-179939
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Bennett DA;Buchman AS;Boyle PA;Barnes LL;Wilson RS;Schneider JA
通讯作者：
Schneider JA
DOI：
10.1073/pnas.1507125112
发表时间：
2015-06-09
影响因子：
11.1
作者：
Darmanis S;Sloan SA;Zhang Y;Enge M;Caneda C;Shuer LM;Hayden Gephart MG;Barres BA;Quake SR
通讯作者：
Quake SR
影响因子：
4.5
作者：
Ghazalpour A;Bennett B;Petyuk VA;Orozco L;Hagopian R;Mungrue IN;Farber CR;Sinsheimer J;Kang HM;Furlotte N;Park CC;Wen PZ;Brewer H;Weitz K;Camp DG 2nd;Pan C;Yordanova R;Neuhaus I;Tilford C;Siemers N;Gargalovic P;Eskin E;Kirchgessner T;Smith DJ;Smith RD;Lusis AJ
通讯作者：
Lusis AJ
影响因子：
4.6
作者：
Hadar A;Milanesi E;Walczak M;Puzianowska-Kuźnicka M;Kuźnicki J;Squassina A;Niola P;Chillotti C;Attems J;Gozes I;Gurwitz D
通讯作者：
Gurwitz D