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

TITLE=Associations of MAP2K3 Gene Variants With Superior Memory in SuperAgers

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=10

YEAR=2018

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2018.00155

DOI=10.3389/fnagi.2018.00155

ISSN=1663-4365

ABSTRACT=<p><bold>Introduction</bold>: SuperAgers are adults age 80+ with episodic memory performance that is <italic>at least</italic> 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).</p><p><bold>Methods</bold>: 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).</p><p><bold>Results</bold>: The SuperAging phenotype was associated with variants in the Mitogen-Activated Protein Kinase Kinase 3 <italic>(MAP2K3)</italic> gene. Three single nucleotide polymorphisms (SNPs) contributed to the significance (rs2363221 [intron 1], rs2230435 [exon 5], rs736103 [intron 7]).</p><p><bold>Conclusions</bold>: 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).</p>