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 language | English (US) |
|---|---|
| Article number | 155 |
| Journal | Frontiers in Aging Neuroscience |
| Volume | 10 |
| Issue number | MAY |
| DOIs | |
| State | Published - May 29 2018 |
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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
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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 journal › Article
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
UR - http://www.scopus.com/inward/record.url?scp=85047668042&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047668042&partnerID=8YFLogxK
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 -