Harmonization of CSF and imaging biomarkers in Alzheimer's disease: Need and practical applications for genetics studies and preclinical classification
In Alzheimer's disease (AD) research, cerebrospinal fluid (CSF) Amyloid beta (Aβ), Tau and pTau are the most accepted and well validated biomarkers. Several methods and platforms exist to measure those biomarkers, leading to challenges in combining data across studies. Thus, there is a need to...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996123003893 |
| _version_ | 1797364206372126720 |
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| author | Jigyasha Timsina Muhammad Ali Anh Do Lihua Wang Daniel Western Yun Ju Sung Carlos Cruchaga |
| author_facet | Jigyasha Timsina Muhammad Ali Anh Do Lihua Wang Daniel Western Yun Ju Sung Carlos Cruchaga |
| author_sort | Jigyasha Timsina |
| collection | DOAJ |
| description | In Alzheimer's disease (AD) research, cerebrospinal fluid (CSF) Amyloid beta (Aβ), Tau and pTau are the most accepted and well validated biomarkers. Several methods and platforms exist to measure those biomarkers, leading to challenges in combining data across studies. Thus, there is a need to identify methods that harmonize and standardize these values. We used a Z-score based approach to harmonize CSF and amyloid imaging data from multiple cohorts and compared GWAS results using this approach with currently accepted methods. We also used a generalized mixture model to calculate the threshold for biomarker-positivity.Based on our findings, our normalization approach performed as well as meta-analysis and did not lead to any spurious results. In terms of dichotomization, cutoffs calculated with this approach were very similar to those reported previously. These findings show that the Z-score based harmonization approach can be applied to heterogeneous platforms and provides biomarker cut-offs consistent with the classical approaches without requiring any additional data. |
| first_indexed | 2024-03-08T16:31:58Z |
| format | Article |
| id | doaj.art-1632babe2c7c49be9046364be9fd5ae3 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-03-08T16:31:58Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-1632babe2c7c49be9046364be9fd5ae32024-01-06T04:38:26ZengElsevierNeurobiology of Disease1095-953X2024-01-01190106373Harmonization of CSF and imaging biomarkers in Alzheimer's disease: Need and practical applications for genetics studies and preclinical classificationJigyasha Timsina0Muhammad Ali1Anh Do2Lihua Wang3Daniel Western4Yun Ju Sung5Carlos Cruchaga6Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63110, USANeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, USADepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author at: Washington University School of Medicine, 4444 Forest Park Ave, St. Louis, MO 63110, USA.In Alzheimer's disease (AD) research, cerebrospinal fluid (CSF) Amyloid beta (Aβ), Tau and pTau are the most accepted and well validated biomarkers. Several methods and platforms exist to measure those biomarkers, leading to challenges in combining data across studies. Thus, there is a need to identify methods that harmonize and standardize these values. We used a Z-score based approach to harmonize CSF and amyloid imaging data from multiple cohorts and compared GWAS results using this approach with currently accepted methods. We also used a generalized mixture model to calculate the threshold for biomarker-positivity.Based on our findings, our normalization approach performed as well as meta-analysis and did not lead to any spurious results. In terms of dichotomization, cutoffs calculated with this approach were very similar to those reported previously. These findings show that the Z-score based harmonization approach can be applied to heterogeneous platforms and provides biomarker cut-offs consistent with the classical approaches without requiring any additional data.http://www.sciencedirect.com/science/article/pii/S0969996123003893HarmonizationZ-scoresBiomarkersImagingAlzheimer'sMeta-analysis |
| spellingShingle | Jigyasha Timsina Muhammad Ali Anh Do Lihua Wang Daniel Western Yun Ju Sung Carlos Cruchaga Harmonization of CSF and imaging biomarkers in Alzheimer's disease: Need and practical applications for genetics studies and preclinical classification Neurobiology of Disease Harmonization Z-scores Biomarkers Imaging Alzheimer's Meta-analysis |
| title | Harmonization of CSF and imaging biomarkers in Alzheimer's disease: Need and practical applications for genetics studies and preclinical classification |
| title_full | Harmonization of CSF and imaging biomarkers in Alzheimer's disease: Need and practical applications for genetics studies and preclinical classification |
| title_fullStr | Harmonization of CSF and imaging biomarkers in Alzheimer's disease: Need and practical applications for genetics studies and preclinical classification |
| title_full_unstemmed | Harmonization of CSF and imaging biomarkers in Alzheimer's disease: Need and practical applications for genetics studies and preclinical classification |
| title_short | Harmonization of CSF and imaging biomarkers in Alzheimer's disease: Need and practical applications for genetics studies and preclinical classification |
| title_sort | harmonization of csf and imaging biomarkers in alzheimer s disease need and practical applications for genetics studies and preclinical classification |
| topic | Harmonization Z-scores Biomarkers Imaging Alzheimer's Meta-analysis |
| url | http://www.sciencedirect.com/science/article/pii/S0969996123003893 |
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