Caspase-1 variant influencing CSF tau and FDG PET levels in non-demented elders from the ADNI cohort
Abstract Background 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...
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | BMC Neurology |
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| Online Access: | https://doi.org/10.1186/s12883-022-02582-9 |
| _version_ | 1819277354068869120 |
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| author | Yi Liu Meng-Shan Tan Zuo-Teng Wang Wei Xu Lan Tan |
| author_facet | Yi Liu Meng-Shan Tan Zuo-Teng Wang Wei Xu Lan Tan |
| author_sort | Yi Liu |
| collection | DOAJ |
| description | Abstract Background 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. Methods Data 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. Results We 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. Conclusions Our study indicated a potential role of Caspase-1 variant in influencing cognitive function might through changing tau related-neurodegeneration process. |
| first_indexed | 2024-12-23T23:54:46Z |
| format | Article |
| id | doaj.art-67981abe512344bbbb9eaef5823ed6a2 |
| institution | Directory Open Access Journal |
| issn | 1471-2377 |
| language | English |
| last_indexed | 2024-12-23T23:54:46Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neurology |
| spelling | doaj.art-67981abe512344bbbb9eaef5823ed6a22022-12-21T17:25:16ZengBMCBMC Neurology1471-23772022-02-012211710.1186/s12883-022-02582-9Caspase-1 variant influencing CSF tau and FDG PET levels in non-demented elders from the ADNI cohortYi Liu0Meng-Shan Tan1Zuo-Teng Wang2Wei Xu3Lan Tan4Department of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Neurology, Qingdao Municipal Hospital, Qingdao UniversityAbstract Background 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. Methods Data 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. Results We 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. Conclusions Our study indicated a potential role of Caspase-1 variant in influencing cognitive function might through changing tau related-neurodegeneration process.https://doi.org/10.1186/s12883-022-02582-9Caspase-1VariantCSFTau pathologyFDG PETNeurodegeneration |
| spellingShingle | Yi Liu Meng-Shan Tan Zuo-Teng Wang Wei Xu Lan Tan Caspase-1 variant influencing CSF tau and FDG PET levels in non-demented elders from the ADNI cohort BMC Neurology Caspase-1 Variant CSF Tau pathology FDG PET Neurodegeneration |
| title | Caspase-1 variant influencing CSF tau and FDG PET levels in non-demented elders from the ADNI cohort |
| title_full | Caspase-1 variant influencing CSF tau and FDG PET levels in non-demented elders from the ADNI cohort |
| title_fullStr | Caspase-1 variant influencing CSF tau and FDG PET levels in non-demented elders from the ADNI cohort |
| title_full_unstemmed | Caspase-1 variant influencing CSF tau and FDG PET levels in non-demented elders from the ADNI cohort |
| title_short | Caspase-1 variant influencing CSF tau and FDG PET levels in non-demented elders from the ADNI cohort |
| title_sort | caspase 1 variant influencing csf tau and fdg pet levels in non demented elders from the adni cohort |
| topic | Caspase-1 Variant CSF Tau pathology FDG PET Neurodegeneration |
| url | https://doi.org/10.1186/s12883-022-02582-9 |
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