Genome-wide association study identifies CBFA2T3 affecting the rate of CSF A β42 decline in non-demented elders.

Genome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ42 decline in non-demented elders. Aging (Albany NY). 2019 Aug 01;11: Authors: Dou KX, Zhang C, Tan CC, Xu W, Li JQ, Cao XP, Tan L, Yu JT, Alzheimer’s Disease Neuroimaging Initiative (ADNI) Abstract 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. PMID: 31370031 [...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research