Correlation Engine 2.0
Clear Search sequence regions

  • african americans (2)
  • brain (1)
  • cognitive (6)
  • dementia (6)
  • Dlgap2 (6)
  • factors (1)
  • female (1)
  • human (2)
  • patients (1)
  • phenotypes (1)
  • protein human (1)
  • rna (1)
  • species (2)
  • species specificity (1)
  • Sizes of these terms reflect their relevance to your search.

    Genetic mechanisms underlying age-related cognitive decline and dementia remain poorly understood. Here, we take advantage of the Diversity Outbred mouse population to utilize quantitative trait loci mapping and identify Dlgap2 as a positional candidate responsible for modifying working memory decline. To evaluate the translational relevance of this finding, we utilize longitudinal cognitive measures from human patients, RNA expression from post-mortem brain tissue, data from a genome-wide association study (GWAS) of Alzheimer's dementia (AD), and GWAS results in African Americans. We find an association between Dlgap2 and AD phenotypes at the variant, gene and protein expression, and methylation levels. Lower cortical DLGAP2 expression is observed in AD and is associated with more plaques and tangles at autopsy and faster cognitive decline. Results will inform future studies aimed at investigating the cross-species role of Dlgap2 in regulating cognitive decline and highlight the benefit of using genetically diverse mice to prioritize novel candidates. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.


    Andrew R Ouellette, Sarah M Neuner, Logan Dumitrescu, Laura C Anderson, Daniel M Gatti, Emily R Mahoney, Jason A Bubier, Gary Churchill, Luanne Peters, Matthew J Huentelman, Jeremy H Herskowitz, Hyun-Sik Yang, Alexandra N Smith, Christiane Reitz, Brian W Kunkle, Charles C White, Philip L De Jager, Julie A Schneider, David A Bennett, Nicholas T Seyfried, Alzheimer’s Disease Genetics Consortium, Elissa J Chesler, Niran Hadad, Timothy J Hohman, Catherine C Kaczorowski. Cross-Species Analyses Identify Dlgap2 as a Regulator of Age-Related Cognitive Decline and Alzheimer's Dementia. Cell reports. 2020 Sep 01;32(9):108091

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 32877673

    View Full Text