Research Paper Volume 11, Issue 15 pp 5433—5444
Genome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ42 decline in non-demented elders
- 1 Department of Neurology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, China
- 2 Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases (MIND), Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
- 3 Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
- 4 Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
received: May 7, 2019 ; accepted: July 21, 2019 ; published: August 1, 2019 ;https://doi.org/10.18632/aging.102125
How to Cite
Copyright © 2019 Dou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Brain amyloid deposition is an early pathological event in Alzheimer’s disease (AD), and abnormally low levels amyloid-β42 peptide (Aβ42) in cerebrospinal fluid (CSF) can be detected in preclinical AD. To identify the genetic determinants that regulate the rate of CSF Aβ42 decline among non-demented elders, we conducted a genome-wide association study involved 321 non-demented elders from Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1/GO/2 cohorts restricted to non-Hispanic Caucasians. A novel genome-wide significant association of higher annualized percent decline of CSF Aβ42 in the gene CBFA2T3 (CBFA2/RUNX1 translocation partner 3; rs13333659-T; p = 2.24 × 10−9) was identified. Besides displaying abnormal CSF Aβ42 levels, rs13333659-T carriers were more likely to exhibit a greater longitudinal cognitive decline (p = 0.029, β = 0.097) and hippocampal atrophy (p = 0.029, β = −0.160) in the non-demented elders, especially for the participants who were amyloid-positive at baseline. These findings suggest rs13333659 in CBFA2T3 as a risk locus to modulate the decline rate of CSF Aβ42 preceding the onset of clinical symptoms.