FASTKD2 is associated with memory and hippocampal structure in older adults
View/ Open
Author
Ramanan, Vijay K
Nho, Kwangsik
Shen, Li
Risacher, Shannon L.
Kim, Sungeun
McDonald, Brenna C.
Farlow, Martin R.
Foroud, Tatiana M.
Gao, Sujuan
Soininen, Hilkka
Kłoszewska, Iwona
Mecocci, Patrizia
Tsolaki, Magda
Vellas, Bruno
Lovestone, Simon
Aisen, Paul S.
Petersen, Ronald C.
Jack, Clifford R.
Shaw, Leslie M.
Trojanowski, John Q.
Weiner, Michael W.
Toga, Arthur W.
Yu, Lei
Bennett, David A.
Saykin, Andrew J.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/mp.2014.142Metadata
Show full item recordCitation
Ramanan, V. K., K. Nho, L. Shen, S. L. Risacher, S. Kim, B. C. McDonald, M. R. Farlow, et al. 2014. “FASTKD2 is associated with memory and hippocampal structure in older adults.” Molecular psychiatry 20 (10): 1197-1204. doi:10.1038/mp.2014.142. http://dx.doi.org/10.1038/mp.2014.142.Abstract
Memory impairment is the cardinal early feature of Alzheimer's disease (AD), 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, EGFR 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427556/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:26860022
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)