Comparative assessment of Alzheimer’s disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study
Introduction: Alzheimer’s disease (AD) is currently defined according to biomarkers reflecting the core underlying neuropathological processes: Aβ deposition, Tau, and neurodegeneration (ATN). The soluble phase of plasma and plasma neuron-derived extracellular vesicles (NDEVs) are increasingly being...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1254834/full |
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| author | Apostolos Manolopoulos Francheska Delgado-Peraza Maja Mustapic Krishna Ananthu Pucha Carlos Nogueras-Ortiz Alexander Daskalopoulos De’Larrian DeAnté Knight Jeannie-Marie Leoutsakos Jeannie-Marie Leoutsakos Esther S. Oh Esther S. Oh Constantine G. Lyketsos Constantine G. Lyketsos Dimitrios Kapogiannis |
| author_facet | Apostolos Manolopoulos Francheska Delgado-Peraza Maja Mustapic Krishna Ananthu Pucha Carlos Nogueras-Ortiz Alexander Daskalopoulos De’Larrian DeAnté Knight Jeannie-Marie Leoutsakos Jeannie-Marie Leoutsakos Esther S. Oh Esther S. Oh Constantine G. Lyketsos Constantine G. Lyketsos Dimitrios Kapogiannis |
| author_sort | Apostolos Manolopoulos |
| collection | DOAJ |
| description | Introduction: Alzheimer’s disease (AD) is currently defined according to biomarkers reflecting the core underlying neuropathological processes: Aβ deposition, Tau, and neurodegeneration (ATN). The soluble phase of plasma and plasma neuron-derived extracellular vesicles (NDEVs) are increasingly being investigated as sources of biomarkers. The aim of this study was to examine the comparative biomarker potential of these two biofluids, as well as the association between respective biomarkers.Methods: We retrospectively identified three distinct diagnostic groups of 44 individuals who provided samples at baseline and at a mean of 3.1 years later; 14 were cognitively unimpaired at baseline and remained so (NRM-NRM), 13 had amnestic MCI that progressed to AD dementia (MCI-DEM) and 17 had AD dementia at both timepoints (DEM-DEM). Plasma NDEVs were isolated by immunoaffinity capture targeting the neuronal markers L1CAM, GAP43, and NLGN3. In both plasma and NDEVs, we assessed ATN biomarkers (Aβ42, Aβ40, total Tau, P181-Tau) alongside several other exploratory markers.Results: The Aβ42/Aβ40 ratio in plasma and NDEVs was lower in MCI-DEM than NRM-NRM at baseline and its levels in NDEVs decreased over time in all three groups. Similarly, plasma and NDEV-associated Aβ42 was lower in MCI-DEM compared to NRM-NRM at baseline and its levels in plasma decreased over time in DEM-DEM. For NDEV-associated proBDNF, compared to NRM-NRM, its levels were lower in MCI-DEM and DEM-DEM at baseline, and they decreased over time in the latter group. No group differences were found for other exploratory markers. NDEV-associated Aβ42/Aβ40 ratio and proBDNF achieved the highest areas under the curve (AUCs) for discriminating between diagnostic groups, while proBDNF was positively associated with Mini-Mental State Examination (MMSE) score. No associations were found between the two biofluids for any assessed marker.Discussion: The soluble phase of plasma and plasma NDEVs demonstrate distinct biomarker profiles both at a single time point and longitudinally. The lack of association between plasma and NDEV measures indicates that the two types of biofluids demonstrate distinct biomarker signatures that may be attributable to being derived through different biological processes. NDEV-associated proBDNF may be a useful biomarker for AD diagnosis and monitoring. |
| first_indexed | 2024-03-11T21:23:23Z |
| format | Article |
| id | doaj.art-d99c325ea7ab40008387a2e22cf924e7 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-11T21:23:23Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-d99c325ea7ab40008387a2e22cf924e72023-09-28T05:28:40ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-09-011010.3389/fmolb.2023.12548341254834Comparative assessment of Alzheimer’s disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control studyApostolos Manolopoulos0Francheska Delgado-Peraza1Maja Mustapic2Krishna Ananthu Pucha3Carlos Nogueras-Ortiz4Alexander Daskalopoulos5De’Larrian DeAnté Knight6Jeannie-Marie Leoutsakos7Jeannie-Marie Leoutsakos8Esther S. Oh9Esther S. Oh10Constantine G. Lyketsos11Constantine G. Lyketsos12Dimitrios Kapogiannis13Intramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United StatesIntramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United StatesIntramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United StatesIntramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United StatesIntramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United StatesIntramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United StatesIntramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United StatesDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, United StatesRichman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, Johns Hopkins School of Medicine, Baltimore, MD, United StatesRichman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDivision of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, United StatesRichman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, Johns Hopkins School of Medicine, Baltimore, MD, United StatesIntramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United StatesIntroduction: Alzheimer’s disease (AD) is currently defined according to biomarkers reflecting the core underlying neuropathological processes: Aβ deposition, Tau, and neurodegeneration (ATN). The soluble phase of plasma and plasma neuron-derived extracellular vesicles (NDEVs) are increasingly being investigated as sources of biomarkers. The aim of this study was to examine the comparative biomarker potential of these two biofluids, as well as the association between respective biomarkers.Methods: We retrospectively identified three distinct diagnostic groups of 44 individuals who provided samples at baseline and at a mean of 3.1 years later; 14 were cognitively unimpaired at baseline and remained so (NRM-NRM), 13 had amnestic MCI that progressed to AD dementia (MCI-DEM) and 17 had AD dementia at both timepoints (DEM-DEM). Plasma NDEVs were isolated by immunoaffinity capture targeting the neuronal markers L1CAM, GAP43, and NLGN3. In both plasma and NDEVs, we assessed ATN biomarkers (Aβ42, Aβ40, total Tau, P181-Tau) alongside several other exploratory markers.Results: The Aβ42/Aβ40 ratio in plasma and NDEVs was lower in MCI-DEM than NRM-NRM at baseline and its levels in NDEVs decreased over time in all three groups. Similarly, plasma and NDEV-associated Aβ42 was lower in MCI-DEM compared to NRM-NRM at baseline and its levels in plasma decreased over time in DEM-DEM. For NDEV-associated proBDNF, compared to NRM-NRM, its levels were lower in MCI-DEM and DEM-DEM at baseline, and they decreased over time in the latter group. No group differences were found for other exploratory markers. NDEV-associated Aβ42/Aβ40 ratio and proBDNF achieved the highest areas under the curve (AUCs) for discriminating between diagnostic groups, while proBDNF was positively associated with Mini-Mental State Examination (MMSE) score. No associations were found between the two biofluids for any assessed marker.Discussion: The soluble phase of plasma and plasma NDEVs demonstrate distinct biomarker profiles both at a single time point and longitudinally. The lack of association between plasma and NDEV measures indicates that the two types of biofluids demonstrate distinct biomarker signatures that may be attributable to being derived through different biological processes. NDEV-associated proBDNF may be a useful biomarker for AD diagnosis and monitoring.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1254834/fullextracellular vesiclesbiomarkersprecision medicineneurodegenerationAlzheimer’s disease |
| spellingShingle | Apostolos Manolopoulos Francheska Delgado-Peraza Maja Mustapic Krishna Ananthu Pucha Carlos Nogueras-Ortiz Alexander Daskalopoulos De’Larrian DeAnté Knight Jeannie-Marie Leoutsakos Jeannie-Marie Leoutsakos Esther S. Oh Esther S. Oh Constantine G. Lyketsos Constantine G. Lyketsos Dimitrios Kapogiannis Comparative assessment of Alzheimer’s disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study Frontiers in Molecular Biosciences extracellular vesicles biomarkers precision medicine neurodegeneration Alzheimer’s disease |
| title | Comparative assessment of Alzheimer’s disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study |
| title_full | Comparative assessment of Alzheimer’s disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study |
| title_fullStr | Comparative assessment of Alzheimer’s disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study |
| title_full_unstemmed | Comparative assessment of Alzheimer’s disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study |
| title_short | Comparative assessment of Alzheimer’s disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study |
| title_sort | comparative assessment of alzheimer s disease related biomarkers in plasma and neuron derived extracellular vesicles a nested case control study |
| topic | extracellular vesicles biomarkers precision medicine neurodegeneration Alzheimer’s disease |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1254834/full |
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