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Front Aging Neurosci. 2018 May 29;10:155. doi: 10.3389/fnagi.2018.00155. eCollection 2018.

Associations of MAP2K3 Gene Variants With Superior Memory in SuperAgers.

Author information

1
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, United States.
2
Cognitive Neurology & Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine (NU FSM), Chicago, IL, United States.
3
Department of Pathology, Northwestern University Feinberg School of Medicine (NU FSM), Chicago, IL, United States.
4
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine (NU FSM), Chicago, IL, United States.
5
Department of Neurology, Northwestern University Feinberg School of Medicine (NU FSM), Chicago, IL, United States.

Abstract

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).

KEYWORDS:

Alzheimer’s; Alzheimer’s dementia; Alzheimer’s disease (AD); aging; cognition; episodic memory; genetics; successful aging; whole exome sequencing

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