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Author Notes:

Correspondence: aliza.wingo@emory.edu

A.P.W. and T.S.W. conceptualized the paper. A.P.W., T.S.W., J.Y., B.L. and W.F. analyzed and interpreted the data. A.P.W. and T.S.W. wrote the original draft. S.M.C., E.S.G., A.L., and B.Y. performed the validation. T.S.W., N.T.S., J.J.L., A.I.L., P.A.B., J.A.S., P.L.D.J., D.A.B. and A.P.W. performed data curation. All authors edited the paper.

We would like to thank the participants of the ROS and MAP studies.

We thank Thanneer Perumal, PhD for creating the estimated cell-type proportions from RNA sequencing data.

The authors declare no competing interests.

Research Funding:

upport for this research was provided by the following grants from the US National Institutes of Health: R01 AG056533 (to A.P.W. and T.S.W.), R01 AG036042 (to D.A.B and P.L.D.J.), R01 AG017917 (to D.A.B.), RF1 AG015819 (to D.A.B.), RC2 AG036547 (to D.A.B.), P30 AG10161 (to D.A.B.), U01 AG46152 (to P.L.D.J.).

A.P.W. was also supported by a grant from the US Veterans Administration (BX003853) and US National Institute of Health U01 MH115484.

T.S.W. was also supported by grants from the US National Institute of Aging (P50 AG025688, R56 AG062256, R56 AG060757, U01 AG061357, U01 AG057195, and RF1 AG051633).


  • Molecular medicine
  • Depression
  • Dimentia
  • Later-life
  • Cognitive trajectory
  • Brain microRNAs
  • RNA sequencing
  • Alzheimer's disease

Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia.

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Journal Title:

NPJ Genomic Medicine


Volume 5, Number 1


, Pages 6-6

Type of Work:

Article | Final Publisher PDF


Late-life depression is associated with an increased risk for dementia but we have limited knowledge of the molecular mechanisms underlying this association. Here we investigated whether brain microRNAs, important posttranscriptional regulators of gene expression, contribute to this association. Late-life depressive symptoms were assessed annually in 300 participants of the Religious Orders Study and Rush Memory and Aging Project for a mean of 7 years. Participants underwent annual cognitive testing, clinical assessment of cognitive status, and uniform neuropathologic examination after death. microRNAs were profiled from the prefrontal cortex using NanoString platform in the discovery cohort and small RNA sequencing in the replication cohort. A global microRNA association study of late-life depressive symptoms was performed using linear mixed model adjusting for the potential confounding factors. Four brain microRNAs were associated with late-life depressive symptoms at adjusted p < 0.05: miR-484, miR-26b-5p, miR-30d-5p, and miR-197-3p. Lower expression levels of these miRNAs were associated having greater depressive symptoms. Furthermore, lower levels of miR-484 and miR-197-3p were associated with faster decline of cognition over time. Moreover, lower miR-484 level was associated with higher probability of having Alzheimer's dementia. Importantly, the associations between miR-484 and depressive symptoms and Alzheimer's dementia, respectively, were replicated in an independent cohort. Lastly, the predicted targets of miR-484 were enriched in a brain protein co-expression module involving synaptic transmission and regulation of synaptic plasticity. This study identified four brain microRNAs associated with late-life depressive symptoms assessed longitudinally. In addition, we found a molecular connection between late-life depression and dementia through miR-484.

Copyright information:

© The Author(s) 2020.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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