FASTKD2 is associated with memory and hippocampal structure in older adults.

TitleFASTKD2 is associated with memory and hippocampal structure in older adults.
Publication TypeJournal Article
Year of Publication2015
AuthorsRamanan, VK, Nho, K, Shen, L, Risacher, SL, McDonald, BC, Farlow, MR, Foroud, TM, Gao, S, Soininen, H, Kloszewska, I, Mecocci, P, Tsolaki, M, Vellas, B, Lovestone, S, Aisen, PS, Petersen, RC, Jack, CR, Shaw, LM, Trojanowski, JQ, Weiner, MW, Green, RC, Toga, AW, De Jager, PL, Yu, L, Bennett, DA, Saykin, AJ
JournalMol Psychiatry
Volume20
Issue10
Pagination1197-204
Date Published2015 Oct
ISSN Number1476-5578
KeywordsAge Factors, Aged, Aged, 80 and over, Alzheimer disease, Female, Genetic Association Studies, Genome-Wide Association Study, Hippocampus, Humans, Longitudinal Studies, Male, Memory, Memory Disorders, Polymorphism, Single Nucleotide, Protein-Serine-Threonine Kinases, Structure-Activity Relationship
Abstract

Memory impairment is the cardinal early feature of Alzheimer's disease, a highly prevalent disorder whose causes remain only partially understood. To identify novel genetic predictors, we used an integrative genomics approach to perform the largest study to date of human memory (n=14 781). Using a genome-wide screen, we discovered a novel association of a polymorphism in the pro-apoptotic gene FASTKD2 (fas-activated serine/threonine kinase domains 2; rs7594645-G) with better memory performance and replicated this finding in independent samples. Consistent with a neuroprotective effect, rs7594645-G carriers exhibited increased hippocampal volume and gray matter density and decreased cerebrospinal fluid levels of apoptotic mediators. The MTOR (mechanistic target of rapamycin) gene and pathways related to endocytosis, cholinergic neurotransmission, epidermal growth factor receptor signaling and immune regulation, among others, also displayed association with memory. These findings nominate FASTKD2 as a target for modulating neurodegeneration and suggest potential mechanisms for therapies to combat memory loss in normal cognitive aging and dementia.

DOI10.1038/mp.2014.142
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/25385369?dopt=Abstract

Endnote Keywords

Genetic analysis/Alzheimer disease/Memory impairment/predictors/FASTKD2

Endnote ID

999999

Alternate JournalMol. Psychiatry
Citation Key8326
PubMed ID25385369
PubMed Central IDPMC4427556
Grant ListK01 AG030514 / AG / NIA NIH HHS / United States
RC4 AG039029 / AG / NIA NIH HHS / United States
RC4AG039029 / AG / NIA NIH HHS / United States
P41 EB015922 / EB / NIBIB NIH HHS / United States
P30AG010129 / AG / NIA NIH HHS / United States
P30 AG010124 / AG / NIA NIH HHS / United States
R01 AG019771 / AG / NIA NIH HHS / United States
S10 RR027710 / RR / NCRR NIH HHS / United States
UL1 RR025761 / RR / NCRR NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
RR020128 / RR / NCRR NIH HHS / United States
R01AG19771 / AG / NIA NIH HHS / United States
R00 LM011384 / LM / NLM NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States
P30 AG010133 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
P30AG10133 / AG / NIA NIH HHS / United States
K99 LM011384 / LM / NLM NIH HHS / United States
U01 AG024904 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01LM011360 / LM / NLM NIH HHS / United States
U24AG21886 / AG / NIA NIH HHS / United States
UL1 TR001108 / TR / NCATS NIH HHS / United States
K01AG030514 / AG / NIA NIH HHS / United States
R01 LM011360 / LM / NLM NIH HHS / United States
C06 RR020128 / RR / NCRR NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
RR027710-01 / RR / NCRR NIH HHS / United States
U01AG009740 / AG / NIA NIH HHS / United States
K01 AG049050 / AG / NIA NIH HHS / United States
RC2 AG036495 / AG / NIA NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
U54 RR025761 / RR / NCRR NIH HHS / United States
R00LM011384 / LM / NLM NIH HHS / United States
RC2AG036495 / AG / NIA NIH HHS / United States