Open AccessGenome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ42 decline in non-demented elders
Author(s) -
KaiXin Dou,
Can Zhang,
Cheng Tan,
Wei Xu,
Jieqiong Li,
XiPeng Cao,
Lan Tan,
JinTai Yu
Publication year - 2019
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.102125
Subject(s) - cerebrospinal fluid , cognitive decline , medicine , dementia , atrophy , genome wide association study , disease , pathological , alzheimer's disease neuroimaging initiative , alzheimer's disease , neuroimaging , amyloid (mycology) , oncology , pathology , gene , biology , psychiatry , single nucleotide polymorphism , genetics , genotype
Brain amyloid deposition is an early pathological event in Alzheimer's disease (AD), and abnormally low levels amyloid-β 42 peptide (Aβ 42 ) in cerebrospinal fluid (CSF) can be detected in preclinical AD. To identify the genetic determinants that regulate the rate of CSF Aβ 42 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 Aβ 42 in the gene CBFA2T3 ( CBFA2/RUNX1 translocation partner 3; rs13333659-T; p = 2.24 × 10 -9 ) was identified. Besides displaying abnormal CSF Aβ 42 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 Aβ 42 preceding the onset of clinical symptoms.