Frontiers in Aging Neuroscience (May 2018)

Associations of MAP2K3 Gene Variants With Superior Memory in SuperAgers

  • Matthew J. Huentelman,
  • Ignazio S. Piras,
  • Ashley L. Siniard,
  • Matthew D. De Both,
  • Ryan F. Richholt,
  • Chris D. Balak,
  • Pouya Jamshidi,
  • Eileen H. Bigio,
  • Eileen H. Bigio,
  • Sandra Weintraub,
  • Sandra Weintraub,
  • Emmaleigh T. Loyer,
  • M.-Marsel Mesulam,
  • M.-Marsel Mesulam,
  • Changiz Geula,
  • Emily J. Rogalski,
  • Emily J. Rogalski

DOI
https://doi.org/10.3389/fnagi.2018.00155
Journal volume & issue
Vol. 10

Abstract

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Introduction: SuperAgers are adults age 80+ with episodic memory performance that is at least as good as that of average middle-aged adults. Understanding the biological determinants of SuperAging may have relevance to preventing age-related cognitive decline and dementia. This study aimed to identify associations between genetic variations and the SuperAging phenotype using Whole Exome Sequencing (WES).Methods: Sequence Kernel Association Combined (SKAT-C) test was conducted at the gene level including both rare and common variants in 56 SuperAgers and 22 cognitively-average controls from the Alzheimer’s disease Neuroimaging Initiative (ADNI).Results: The SuperAging phenotype was associated with variants in the Mitogen-Activated Protein Kinase Kinase 3 (MAP2K3) gene. Three single nucleotide polymorphisms (SNPs) contributed to the significance (rs2363221 [intron 1], rs2230435 [exon 5], rs736103 [intron 7]).Conclusions: MAP2K3 resides in a biological pathway linked to memory. It is in a signaling cascade associated with beta-amyloid mediated apoptosis and has enriched expression in microglia. This preliminary work suggests MAP2K3 may represent a novel therapeutic target for age-related memory decline and perhaps Alzheimer’s disease (AD).

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