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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Main Authors: Hyung Joon Cho, Philip Schulz, Lalitha Venkataraman, Richard J. Caselli, Michael R. Sierks
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:International Journal of Molecular Sciences
Subjects:
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.
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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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