Dataset Information

Genome-wide association study identifies CD1A associated with rate of increase in plasma neurofilament light in non-demented elders.

ABSTRACT: As a marker of neuroaxonal injury, neurofilament light (NFL) in blood is robustly elevated in many neurodegenerative conditions. We aimed to discover single nucleotide polymorphisms (SNPs) associated with longitudinal changes in plasma NFL levels that affect the risk of developing neurodegenerative disease and clinical disease progression. 545 eligible non-Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with longitudinal plasma NFL data were included. Three SNPs (rs16840041, p=4.50×10-8; rs2269714, p=4.50×10-8; rs2269715, p=4.83×10-8) in CD1A were in high linkage disequilibrium (LD) and significantly associated with the increase in plasma NFL levels. We demonstrate a promoting effect of rs16840041-A on clinical disease progression (p = 0.006). Moreover, the minor allele (A) of rs16840041 was significantly associated with accelerated decline in [18F] Fluorodeoxyglucose (FDG) (estimate -1.6% per year [95% CI -0.6 to -2.6], p=0.0024). CD1A is a gene involved in longitudinal changes in plasma NFL levels and AD-related phenotypes among non-demented elders. Given the potential effects of these variants, CD1A should be further investigated as a gene of interest in neurodegenerative diseases and as a potential target for monitoring disease trajectories and treating disease.

SUBMITTER: Wang ZT

PROVIDER: S-EPMC6660034 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide association study identifies CD1A associated with rate of increase in plasma neurofilament light in non-demented elders.

Wang Zuo-Teng ZT Chen Shi-Dong SD Xu Wei W Chen Ke-Liang KL Wang Hui-Fu HF Tan Chen-Chen CC Cui Mei M Dong Qiang Q Tan Lan L Yu Jin-Tai JT

Aging 20190701 13

As a marker of neuroaxonal injury, neurofilament light (NFL) in blood is robustly elevated in many neurodegenerative conditions. We aimed to discover single nucleotide polymorphisms (SNPs) associated with longitudinal changes in plasma NFL levels that affect the risk of developing neurodegenerative disease and clinical disease progression. 545 eligible non-Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with longitudinal plasma NFL data were included. Thre ...[more]

PMID: 31295725

Similar Datasets

Project description:While delirium is associated with cognitive decline and dementia, there is limited evidence to support causality for this relationship. Clarification of how delirium may cause cognitive decline, perhaps through evidence of contemporaneous neuronal injury, would enhance plausibility for a causal relationship. Dose-dependence of neuronal injury with delirium severity would further enhance the biological plausibility for this relationship. We tested whether delirium is associated with neuronal injury in 114 surgical patients recruited to a prospective biomarker cohort study. Patients underwent perioperative testing for changes in neurofilament light, a neuronal injury biomarker, as well as a panel of 10 cytokines, with contemporaneous assessment of delirium severity and incidence. A subset of patients underwent preoperative MRI. Initially we confirmed prior reports that neurofilament light levels correlated with markers of neurodegeneration [hippocampal volume (ΔR2 = 0.129, P = 0.015)] and white matter changes including fractional anisotropy of white matter (ΔR2 = 0.417, P < 0.001) with similar effects on mean, axial and radial diffusivity) in our cohort and that surgery was associated with increasing neurofilament light from preoperative levels [mean difference (95% confidence interval, CI) = 0.240 (0.178, 0.301) log10 (pg/ml), P < 0.001], suggesting putative neuronal injury. Next, we tested the relationship with delirium. Neurofilament light rose more sharply in participants with delirium compared to non-sufferers [mean difference (95% CI) = 0.251 (0.136, 0.367) log10 (pg/ml), P < 0.001]. This relationship showed dose-dependence, such that neurofilament light rose proportionately to delirium severity (ΔR2 = 0.199, P < 0.001). Given that inflammation is considered an important driver of postoperative delirium, next we tested whether neurofilament light, as a potential marker of neurotoxicity, may contribute to the pathogenesis of delirium independent of inflammation. From a panel of 10 cytokines, the pro-inflammatory cytokine IL-8 exhibited a strong correlation with delirium severity (ΔR2 = 0.208, P < 0.001). Therefore, we tested whether the change in neurofilament light contributed to delirium severity independent of IL-8. Neurofilament light was independently associated with delirium severity after adjusting for the change in inflammation (ΔR2 = 0.040, P = 0.038). These data suggest delirium is associated with exaggerated increases in neurofilament light and that this putative neurotoxicity may contribute to the pathogenesis of delirium itself, independent of changes in inflammation.

Dataset Information

Genome-wide association study identifies CD1A associated with rate of increase in plasma neurofilament light in non-demented elders.

Publications

Genome-wide association study identifies CD1A associated with rate of increase in plasma neurofilament light in non-demented elders.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets