Caspase-1 variant influencing CSF tau and FDG PET levels in non-demented elders from the ADNI cohort

Yi Liu,Meng-Shan Tan,Lan Tan,Wei Xu,Zuo-Teng Wang

doi:10.1186/s12883-022-02582-9

Yi Liu, Meng-Shan Tan + Show 3 more

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https://doi.org/10.1186/s12883-022-02582-9

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Journal: BMC Neurology	Publication Date: Feb 16, 2022
Citations: 1	License type: open-access

Affiliation: Qingdao Municipal Hospital, Qingdao University

Abstract

BackgroundGenetic variations in the inflammatory Caspase-1 gene have been shown associated with cognitive function in elderly individuals and in predisposition to Alzheimer’s disease (AD), but its detailed mechanism before the typical AD onset was still unclear. Our current study evaluated the impact of Caspase-1 common variant rs554344 on the pathological processes of brain amyloidosis, tauopathy, and neurodegeneration.MethodsData used in our study were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. We examined the relationship between Caspase-1 rs554344 allele carrier status with AD-related cerebrospinal fluid (CSF), PET, and MRI measures at baseline by using a multiple linear regression model. We also analyzed the longitudinal effects of this variant on the change rates of CSF biomarkers and imaging data using a mixed effect model.ResultsWe found that Caspase-1 variant was significantly associated with FDG PET levels and CSF t-tau levels at baseline in total non-demented elderly group, and especially in mild cognitive impairment (MCI) subgroup. In addition, this variant was also detected associated with CSF p-tau levels in MCI subgroup. The mediation analysis showed that CSF p-tau partially mediated the association between Caspase-1 variant and CSF t-tau levels, accounting for 80% of the total effect.ConclusionsOur study indicated a potential role of Caspase-1 variant in influencing cognitive function might through changing tau related-neurodegeneration process.

Highlights

Genetic variations in the inflammatory Caspase-1 gene have been shown associated with cognitive function in elderly individuals and in predisposition to Alzheimer’s disease (AD), but its detailed mechanism before the typical AD onset was still unclear
Our current study examined the impact of Caspase-1 variant rs554344 on the pathological processes of brain amyloidosis, tauopathy, and neurodegeneration, using the baseline and follow-up data from AD-related cerebrospinal fluid (CSF), Positron-emission tomog‐ raphy (PET), and MRI measures in a large non-demented population, including normal cognition (NC) and mild cognitive impairment (MCI) subgroups, from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database
Our results demonstrated that Caspase-1 loci genotype was significantly associated with CSF t-tau (β Coefficient and 95% confidence interval (CI) = − 0.068 (− 0.134 – − 0.002), p < 0.05) and FDG PET levels (β Coefficient and 95% CI = − 0.026 (− 0.46 – − 0.06), Table 2 The correlation between Caspase-1 rs554344 and CSF biomarkers, imaging data at baseline in a multiple linear regression model

Summary

Introduction

Genetic variations in the inflammatory Caspase-1 gene have been shown associated with cognitive function in elderly individuals and in predisposition to Alzheimer’s disease (AD), but its detailed mechanism before the typical AD onset was still unclear. Our current study evaluated the impact of Caspase-1 common variant rs554344 on the pathological processes of brain amyloidosis, tauopathy, and neurodegeneration. Our current study examined the impact of Caspase-1 variant rs554344 on the pathological processes of brain amyloidosis, tauopathy, and neurodegeneration, using the baseline and follow-up data from AD-related CSF, PET, and MRI measures in a large non-demented population, including normal cognition (NC) and MCI subgroups, from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database The new guidelines, better known as the NIA-AA research framework, could be used for observational and interventional research, which defines AD by three biomarkers in living person: β-amyloid (Aβ) deposition, including amyloid-PET, CSF Aβ42 or Aβ42/Aβ40 ratio; pathologic tau, including tauPET, CSF phosphorylated tau (p-tau); Neurodegeneration, including fluorodeoxyglucose (FDG) PET, CSF total tau (t-tau) or brain structural MRI.

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