Genome-wide association study identifies CBFA2T3 affecting the rate of CSF A?42 decline in non-demented elders.

ABSTRACT: Brain amyloid deposition is an early pathological event in Alzheimer's disease (AD), and abnormally low levels amyloid-?42 peptide (A?42) in cerebrospinal fluid (CSF) can be detected in preclinical AD. To identify the genetic determinants that regulate the rate of CSF A?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 A?42 in the gene CBFA2T3 (CBFA2/RUNX1 translocation partner 3; rs13333659-T; p = 2.24 × 10-9) was identified. Besides displaying abnormal CSF A?42 levels, rs13333659-T carriers were more likely to exhibit a greater longitudinal cognitive decline (p = 0.029, ? = 0.097) and hippocampal atrophy (p = 0.029, ? = -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 A?42 preceding the onset of clinical symptoms.

SUBMITTER: Dou KX 

PROVIDER: S-EPMC6710044 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature