Neuronal-Derived EV Biomarkers Track Cognitive Decline in Alzheimer’s Disease
The hallmarks of Alzheimer’s disease (AD) pathology are senile plaques containing amyloid-beta (Aβ) and neurofibrillary tangles containing hyperphosphorylated tau. Additional pathologies often co-exist, whereas multiple pathogenic mechanisms are involved in AD, especially synaptic degeneration, whic...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/3/436 |
| _version_ | 1797488486652051456 |
|---|---|
| author | Erden Eren Jeannie-Marie Leoutsakos Juan Troncoso Constantine G. Lyketsos Esther S. Oh Dimitrios Kapogiannis |
| author_facet | Erden Eren Jeannie-Marie Leoutsakos Juan Troncoso Constantine G. Lyketsos Esther S. Oh Dimitrios Kapogiannis |
| author_sort | Erden Eren |
| collection | DOAJ |
| description | The hallmarks of Alzheimer’s disease (AD) pathology are senile plaques containing amyloid-beta (Aβ) and neurofibrillary tangles containing hyperphosphorylated tau. Additional pathologies often co-exist, whereas multiple pathogenic mechanisms are involved in AD, especially synaptic degeneration, which necessitate the need for synaptic integrity-related biomarkers alongside Aβ- and tau-related biomarkers. Plasma neuron-derived Extracellular Vesicles EVs (NDEVs) provide biomarkers related to Aβ and tau and synaptic degeneration. Here, to further establish the latter as a “liquid biopsy” for AD, we examined their relationship with ante-mortem cognition in pathologically-confirmed AD cases. We immunoprecipitated NDEVs by targeting neuronal marker L1CAM from ante-mortem plasma samples from 61 autopsy-confirmed cases of pure AD or AD with additional pathologies and measured Aβ<sub>42</sub>, p181-Tau, total Tau, synaptophysin, synaptopodin and three canonical EV markers, CD63, CD81 and CD9. Higher NDEV Aβ<sub>42</sub> levels were consistently associated with better cognitive status, memory, fluency, working memory and executive function. Higher levels of NDEV synaptic integrity-related biomarkers were associated with better performance on executive function tasks. Our findings motivate the hypothesis that releasing Aβ<sub>42</sub>-laden NDEVs may be an adaptive mechanism in AD. |
| first_indexed | 2024-03-10T00:03:54Z |
| format | Article |
| id | doaj.art-015bb8b298c54e5ea415597b6cb6e56d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:03:54Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-015bb8b298c54e5ea415597b6cb6e56d2023-11-23T16:11:50ZengMDPI AGCells2073-44092022-01-0111343610.3390/cells11030436Neuronal-Derived EV Biomarkers Track Cognitive Decline in Alzheimer’s DiseaseErden Eren0Jeannie-Marie Leoutsakos1Juan Troncoso2Constantine G. Lyketsos3Esther S. Oh4Dimitrios Kapogiannis5Intramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD 21224, USADepartment of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USADepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21224, USADepartment of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USADepartment of Medicine, Division of Geriatric Medicine and Gerontology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USAIntramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD 21224, USAThe hallmarks of Alzheimer’s disease (AD) pathology are senile plaques containing amyloid-beta (Aβ) and neurofibrillary tangles containing hyperphosphorylated tau. Additional pathologies often co-exist, whereas multiple pathogenic mechanisms are involved in AD, especially synaptic degeneration, which necessitate the need for synaptic integrity-related biomarkers alongside Aβ- and tau-related biomarkers. Plasma neuron-derived Extracellular Vesicles EVs (NDEVs) provide biomarkers related to Aβ and tau and synaptic degeneration. Here, to further establish the latter as a “liquid biopsy” for AD, we examined their relationship with ante-mortem cognition in pathologically-confirmed AD cases. We immunoprecipitated NDEVs by targeting neuronal marker L1CAM from ante-mortem plasma samples from 61 autopsy-confirmed cases of pure AD or AD with additional pathologies and measured Aβ<sub>42</sub>, p181-Tau, total Tau, synaptophysin, synaptopodin and three canonical EV markers, CD63, CD81 and CD9. Higher NDEV Aβ<sub>42</sub> levels were consistently associated with better cognitive status, memory, fluency, working memory and executive function. Higher levels of NDEV synaptic integrity-related biomarkers were associated with better performance on executive function tasks. Our findings motivate the hypothesis that releasing Aβ<sub>42</sub>-laden NDEVs may be an adaptive mechanism in AD.https://www.mdpi.com/2073-4409/11/3/436extracellular vesiclesautopsyAlzheimer’s diseasemixed pathologyexosomesneuron-derived extracellular vesicles |
| spellingShingle | Erden Eren Jeannie-Marie Leoutsakos Juan Troncoso Constantine G. Lyketsos Esther S. Oh Dimitrios Kapogiannis Neuronal-Derived EV Biomarkers Track Cognitive Decline in Alzheimer’s Disease Cells extracellular vesicles autopsy Alzheimer’s disease mixed pathology exosomes neuron-derived extracellular vesicles |
| title | Neuronal-Derived EV Biomarkers Track Cognitive Decline in Alzheimer’s Disease |
| title_full | Neuronal-Derived EV Biomarkers Track Cognitive Decline in Alzheimer’s Disease |
| title_fullStr | Neuronal-Derived EV Biomarkers Track Cognitive Decline in Alzheimer’s Disease |
| title_full_unstemmed | Neuronal-Derived EV Biomarkers Track Cognitive Decline in Alzheimer’s Disease |
| title_short | Neuronal-Derived EV Biomarkers Track Cognitive Decline in Alzheimer’s Disease |
| title_sort | neuronal derived ev biomarkers track cognitive decline in alzheimer s disease |
| topic | extracellular vesicles autopsy Alzheimer’s disease mixed pathology exosomes neuron-derived extracellular vesicles |
| url | https://www.mdpi.com/2073-4409/11/3/436 |
| work_keys_str_mv | AT erdeneren neuronalderivedevbiomarkerstrackcognitivedeclineinalzheimersdisease AT jeanniemarieleoutsakos neuronalderivedevbiomarkerstrackcognitivedeclineinalzheimersdisease AT juantroncoso neuronalderivedevbiomarkerstrackcognitivedeclineinalzheimersdisease AT constantineglyketsos neuronalderivedevbiomarkerstrackcognitivedeclineinalzheimersdisease AT esthersoh neuronalderivedevbiomarkerstrackcognitivedeclineinalzheimersdisease AT dimitrioskapogiannis neuronalderivedevbiomarkerstrackcognitivedeclineinalzheimersdisease |