Associations of MAP2K3 gene variants with superior memory in SuperAgers

for the Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

3 Citations (Scopus)

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).

Original languageEnglish (US)
Article number155
JournalFrontiers in Aging Neuroscience
Volume10
Issue numberMAY
DOIs
StatePublished - May 29 2018

Fingerprint

Introns
Alzheimer Disease
MAP Kinase Kinase 3
Exome
Phenotype
Episodic Memory
Microglia
Amyloid
Neuroimaging
Genes
Single Nucleotide Polymorphism
Dementia
Exons
Apoptosis
Therapeutics
Cognitive Dysfunction

Keywords

  • Aging
  • Alzheimer's
  • Alzheimer's dementia
  • Alzheimer's disease (AD)
  • Cognition
  • Episodic memory
  • Genetics
  • Successful aging
  • Whole exome sequencing

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience

Cite this

for the Alzheimer's Disease Neuroimaging Initiative. / Associations of MAP2K3 gene variants with superior memory in SuperAgers. In: Frontiers in Aging Neuroscience. 2018 ; Vol. 10, No. MAY.
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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).",
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Associations of MAP2K3 gene variants with superior memory in SuperAgers. / for the Alzheimer's Disease Neuroimaging Initiative.

In: Frontiers in Aging Neuroscience, Vol. 10, No. MAY, 155, 29.05.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Associations of MAP2K3 gene variants with superior memory in SuperAgers

AU - for the Alzheimer's Disease Neuroimaging Initiative

AU - Huentelman, Matthew J.

AU - Piras, Ignazio S.

AU - Siniard, Ashley L.

AU - De Both, Matthew D.

AU - Richholt, Ryan F.

AU - Balak, Chris D.

AU - Jamshidi, Pouya

AU - Bigio, Eileen H

AU - Weintraub, Sandra

AU - Loyer, Emmaleigh T.

AU - Mesulam, Marek-Marsel

AU - Geula, Changiz

AU - Rogalski, Emily

PY - 2018/5/29

Y1 - 2018/5/29

N2 - 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).

AB - 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).

KW - Aging

KW - Alzheimer's

KW - Alzheimer's dementia

KW - Alzheimer's disease (AD)

KW - Cognition

KW - Episodic memory

KW - Genetics

KW - Successful aging

KW - Whole exome sequencing

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U2 - 10.3389/fnagi.2018.00155

DO - 10.3389/fnagi.2018.00155

M3 - Article

C2 - 29896098

AN - SCOPUS:85047668042

VL - 10

JO - Frontiers in Aging Neuroscience

JF - Frontiers in Aging Neuroscience

SN - 1663-4365

IS - MAY

M1 - 155

ER -