Sex-Specific Multiparameter Blood Test for the Early Diagnosis of Alzheimer’s Disease
Blood-based biomarkers are needed for the early diagnosis of Alzheimer’s disease (AD). We analyzed longitudinal human plasma samples from AD and control cases to identify biomarkers for the early diagnosis of AD. Plasma samples were grouped based on clinical diagnosis at the time of collection: AD,...
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MDPI AG
2022-12-01
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Series: | International Journal of Molecular Sciences |
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Online Access: | https://www.mdpi.com/1422-0067/23/24/15670 |
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author | Hyung Joon Cho Philip Schulz Lalitha Venkataraman Richard J. Caselli Michael R. Sierks |
author_facet | Hyung Joon Cho Philip Schulz Lalitha Venkataraman Richard J. Caselli Michael R. Sierks |
author_sort | Hyung Joon Cho |
collection | DOAJ |
description | Blood-based biomarkers are needed for the early diagnosis of Alzheimer’s disease (AD). We analyzed longitudinal human plasma samples from AD and control cases to identify biomarkers for the early diagnosis of AD. Plasma samples were grouped based on clinical diagnosis at the time of collection: AD, mild cognitive impairment (MCI), and pre-symptomatic (preMCI). Samples were analyzed by ELISA using a panel of reagents against nine different AD-related amyloid-β (Aβ), tau, or TDP-43 variants. Receiver operating characteristic (ROC) curves of different biomarker panels for different diagnostic sample groups were determined. Analysis of all of the samples gave a sensitivity of 92% and specificity of 76% for the diagnosis of AD. Early-stage diagnosis of AD, utilizing only the preMCI and MCI samples, identified 88% of AD cases. Using sex-biased biomarker panels, early diagnosis of AD cases improved to 96%. Using the sex-biased panels, we also identified 6 of the 25 control group cases as being at high risk of AD, which is consistent with what is expected given the advanced age of the control cases. Specific AD-associated protein variants are effective blood-based biomarkers for the early diagnosis of AD. Notably, significant differences were observed in biomarker profiles for the early detection of male and female AD cases. |
first_indexed | 2024-03-09T16:19:25Z |
format | Article |
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institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T16:19:25Z |
publishDate | 2022-12-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-16cfba21a7bd4ad291ec77ddf0efbce42023-11-24T15:25:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241567010.3390/ijms232415670Sex-Specific Multiparameter Blood Test for the Early Diagnosis of Alzheimer’s DiseaseHyung Joon Cho0Philip Schulz1Lalitha Venkataraman2Richard J. Caselli3Michael R. Sierks4Department of Internal Medicine, The University of Arizona College of Medicine—Phoenix, Phoenix, AZ 85004, USAChemical Engineering, School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ 85287, USACenter for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH 43205, USADepartment of Neurology, Mayo Clinic, Scottsdale, AZ 85259, USAChemical Engineering, School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ 85287, USABlood-based biomarkers are needed for the early diagnosis of Alzheimer’s disease (AD). We analyzed longitudinal human plasma samples from AD and control cases to identify biomarkers for the early diagnosis of AD. Plasma samples were grouped based on clinical diagnosis at the time of collection: AD, mild cognitive impairment (MCI), and pre-symptomatic (preMCI). Samples were analyzed by ELISA using a panel of reagents against nine different AD-related amyloid-β (Aβ), tau, or TDP-43 variants. Receiver operating characteristic (ROC) curves of different biomarker panels for different diagnostic sample groups were determined. Analysis of all of the samples gave a sensitivity of 92% and specificity of 76% for the diagnosis of AD. Early-stage diagnosis of AD, utilizing only the preMCI and MCI samples, identified 88% of AD cases. Using sex-biased biomarker panels, early diagnosis of AD cases improved to 96%. Using the sex-biased panels, we also identified 6 of the 25 control group cases as being at high risk of AD, which is consistent with what is expected given the advanced age of the control cases. Specific AD-associated protein variants are effective blood-based biomarkers for the early diagnosis of AD. Notably, significant differences were observed in biomarker profiles for the early detection of male and female AD cases.https://www.mdpi.com/1422-0067/23/24/15670Alzheimer’s diseaseamyloid-βtauTDP-43longitudinal biomarkerblood-based diagnostic |
spellingShingle | Hyung Joon Cho Philip Schulz Lalitha Venkataraman Richard J. Caselli Michael R. Sierks Sex-Specific Multiparameter Blood Test for the Early Diagnosis of Alzheimer’s Disease International Journal of Molecular Sciences Alzheimer’s disease amyloid-β tau TDP-43 longitudinal biomarker blood-based diagnostic |
title | Sex-Specific Multiparameter Blood Test for the Early Diagnosis of Alzheimer’s Disease |
title_full | Sex-Specific Multiparameter Blood Test for the Early Diagnosis of Alzheimer’s Disease |
title_fullStr | Sex-Specific Multiparameter Blood Test for the Early Diagnosis of Alzheimer’s Disease |
title_full_unstemmed | Sex-Specific Multiparameter Blood Test for the Early Diagnosis of Alzheimer’s Disease |
title_short | Sex-Specific Multiparameter Blood Test for the Early Diagnosis of Alzheimer’s Disease |
title_sort | sex specific multiparameter blood test for the early diagnosis of alzheimer s disease |
topic | Alzheimer’s disease amyloid-β tau TDP-43 longitudinal biomarker blood-based diagnostic |
url | https://www.mdpi.com/1422-0067/23/24/15670 |
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