Shared Biologic Pathways Between Alzheimer Disease and Major Depression: A Systematic Review of MicroRNA Expression Studies

Ana Paula Mendes-Silva, Kelly Silva Pereira, Gesiane Thamire Tolentino-Araujo, Eduardo de Souza Nicolau, Camila Moreira Silva-Ferreira, Antonio Lucio Teixeira, Breno S. Diniz

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Objective The clinical–epidemiological relationship between major depressive disorder (MDD) and Alzheimer disease (AD) suggests that they may share common neurobiologic abnormalities. Methods The authors conducted a systematic review and identified microRNAs abnormally expressed in both AD and MDD. The pattern of microRNA regulation in each disorder and the genes regulated by each microRNA and the biologic processes and pathways regulated by these genes were identified. Results Seventy-four microRNAs were abnormally expressed in AD and 30 in MDD; 7 were common for both disorders (hsa-let-7f-5p, hsa-miR-664a-3p, hsa-miR-361-5p, hsa-let-7g-5p, hsa-let-7d-5p, hsa-miR-191-5p, hsa-miR-26b-5p). These microRNAs interact with 45 validated genes, and the main biologic pathways and processes regulated by them were proteostasis control, maintenance of genomic integrity, regulation of transcriptional activity, immune-inflammatory control, and neurotrophic support. Conclusion The current results suggest that the maintenance of genomic integrity, proteostasis control, immune-inflammatory regulation, and neurotrophic support are key neurobiologic links between these conditions. A comprehensive hypothetical model for the interaction between MDD, aging, and the development of AD is provided.

Original languageEnglish (US)
Pages (from-to)903-912
Number of pages10
JournalAmerican Journal of Geriatric Psychiatry
Issue number10
StatePublished - Oct 1 2016
Externally publishedYes


  • Alzheimer disease
  • biologic pathways
  • biomarkers
  • geriatric depression
  • major depressive disorder
  • microRNAs

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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