Effect of renal function on the diagnostic performance of plasma biomarkers for Alzheimer’s disease
BackgroundSeveral blood-based biomarkers are promising to be used in the diagnosis of Alzheimer’s disease (AD) including Aβ42/40, p-tau181, and neurofilament light (NfL). The kidney is associated with the clearance of proteins. It is crucial to evaluate the effect of renal function on the diagnostic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1150510/full |
| _version_ | 1797870454644408320 |
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| author | Bin Zhang Cheng Zhang YuYe Wang LeiAn Chen YaNan Qiao Yu Wang DanTao Peng for the Alzheimer’s Disease Neuroimaging Initiative |
| author_facet | Bin Zhang Cheng Zhang YuYe Wang LeiAn Chen YaNan Qiao Yu Wang DanTao Peng for the Alzheimer’s Disease Neuroimaging Initiative |
| author_sort | Bin Zhang |
| collection | DOAJ |
| description | BackgroundSeveral blood-based biomarkers are promising to be used in the diagnosis of Alzheimer’s disease (AD) including Aβ42/40, p-tau181, and neurofilament light (NfL). The kidney is associated with the clearance of proteins. It is crucial to evaluate the effect of renal function on the diagnostic performance of these biomarkers before clinical implementation, which is important for the establishment of reference ranges and the interpretation of results.MethodsThis study is a cross-sectional analysis based on ADNI cohort. Renal function was determined by the estimated glomerular filtration rate (eGFR). Plasma Aβ42/40 was measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Plasma p-tau181 and NfL were analyzed by Single Molecule array (Simoa) technique. [18F] florbetapir-PET (Aβ-PET) was used as a reference standard to estimate the brain amyloid load. The cutoff of Aβ-PET positivity was defined as ≥1.11. Linear regression models were used to investigate the associations of continuous eGFR with each plasma biomarker separately. The diagnostic accuracies of plasma biomarkers for positive brain amyloid across different renal function groups were analyzed by Receiver operating characteristic (ROC) curve. Youden-Index was used to determine the cutoff levels.ResultsA total of 645 participants were included in this study. The levels and diagnostic performance of Aβ42/40 were not affected by renal function. eGFR was only found negatively associated with p-tau181 levels in Aβ-PET negetive sample (β = −0.09, p = 0.039). eGFR was found negatively associated with NfL levels both in whole sample and Aβ-PET stratified groups (β = −0.27, p < 0.001 in whole sample; β = −0.28, p = 0.004 in A−; β = −0.27, p < 0.001 in A+). The diagnostic accuracies of p-tau181 and NfL were not affected by renal function. But the cutoff values of p-tau181 and NfL changed in participants with mild to moderate eGFR decline compared to participants with normal eGFR.ConclusionPlasma Aβ42/40 was a robust biomarker for AD which was not affected by renal function. Plasma p-tau181 and NfL levels were affected by renal function, specific reference values of them should be considered in populations with different renal function stages. |
| first_indexed | 2024-04-10T00:27:45Z |
| format | Article |
| id | doaj.art-6fbc8f9ca8304d308347c440686f9d62 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-10T00:27:45Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-6fbc8f9ca8304d308347c440686f9d622023-03-15T05:52:50ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-03-011510.3389/fnagi.2023.11505101150510Effect of renal function on the diagnostic performance of plasma biomarkers for Alzheimer’s diseaseBin Zhang0Cheng Zhang1YuYe Wang2LeiAn Chen3YaNan Qiao4Yu Wang5DanTao Peng6for the Alzheimer’s Disease Neuroimaging InitiativeDepartment of Neurology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaSchool of Acupuncture, Moxibustion and Tuina, International Acupuncture and Moxibustion Innovation Institute, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBackgroundSeveral blood-based biomarkers are promising to be used in the diagnosis of Alzheimer’s disease (AD) including Aβ42/40, p-tau181, and neurofilament light (NfL). The kidney is associated with the clearance of proteins. It is crucial to evaluate the effect of renal function on the diagnostic performance of these biomarkers before clinical implementation, which is important for the establishment of reference ranges and the interpretation of results.MethodsThis study is a cross-sectional analysis based on ADNI cohort. Renal function was determined by the estimated glomerular filtration rate (eGFR). Plasma Aβ42/40 was measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Plasma p-tau181 and NfL were analyzed by Single Molecule array (Simoa) technique. [18F] florbetapir-PET (Aβ-PET) was used as a reference standard to estimate the brain amyloid load. The cutoff of Aβ-PET positivity was defined as ≥1.11. Linear regression models were used to investigate the associations of continuous eGFR with each plasma biomarker separately. The diagnostic accuracies of plasma biomarkers for positive brain amyloid across different renal function groups were analyzed by Receiver operating characteristic (ROC) curve. Youden-Index was used to determine the cutoff levels.ResultsA total of 645 participants were included in this study. The levels and diagnostic performance of Aβ42/40 were not affected by renal function. eGFR was only found negatively associated with p-tau181 levels in Aβ-PET negetive sample (β = −0.09, p = 0.039). eGFR was found negatively associated with NfL levels both in whole sample and Aβ-PET stratified groups (β = −0.27, p < 0.001 in whole sample; β = −0.28, p = 0.004 in A−; β = −0.27, p < 0.001 in A+). The diagnostic accuracies of p-tau181 and NfL were not affected by renal function. But the cutoff values of p-tau181 and NfL changed in participants with mild to moderate eGFR decline compared to participants with normal eGFR.ConclusionPlasma Aβ42/40 was a robust biomarker for AD which was not affected by renal function. Plasma p-tau181 and NfL levels were affected by renal function, specific reference values of them should be considered in populations with different renal function stages.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1150510/fullAlzheimer’s diseaseplasma biomarkersrenal functiondiagnostic performancecutoff |
| spellingShingle | Bin Zhang Cheng Zhang YuYe Wang LeiAn Chen YaNan Qiao Yu Wang DanTao Peng for the Alzheimer’s Disease Neuroimaging Initiative Effect of renal function on the diagnostic performance of plasma biomarkers for Alzheimer’s disease Frontiers in Aging Neuroscience Alzheimer’s disease plasma biomarkers renal function diagnostic performance cutoff |
| title | Effect of renal function on the diagnostic performance of plasma biomarkers for Alzheimer’s disease |
| title_full | Effect of renal function on the diagnostic performance of plasma biomarkers for Alzheimer’s disease |
| title_fullStr | Effect of renal function on the diagnostic performance of plasma biomarkers for Alzheimer’s disease |
| title_full_unstemmed | Effect of renal function on the diagnostic performance of plasma biomarkers for Alzheimer’s disease |
| title_short | Effect of renal function on the diagnostic performance of plasma biomarkers for Alzheimer’s disease |
| title_sort | effect of renal function on the diagnostic performance of plasma biomarkers for alzheimer s disease |
| topic | Alzheimer’s disease plasma biomarkers renal function diagnostic performance cutoff |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1150510/full |
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