Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis
Abstract Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer’s disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and pro...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-024-01727-w |
| _version_ | 1797272845232898048 |
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| author | Zhen Guo Chen Tian Yang Shi Xue-Ru Song Wei Yin Qing-Qing Tao Jie Liu Guo-Ping Peng Zhi-Ying Wu Yan-Jiang Wang Zhen-Xin Zhang Jing Zhang |
| author_facet | Zhen Guo Chen Tian Yang Shi Xue-Ru Song Wei Yin Qing-Qing Tao Jie Liu Guo-Ping Peng Zhi-Ying Wu Yan-Jiang Wang Zhen-Xin Zhang Jing Zhang |
| author_sort | Zhen Guo |
| collection | DOAJ |
| description | Abstract Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer’s disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD and GPR162 were identified as novel brain regionally enriched plasma EVs markers. The performance of GABRD and GPR162, along with the AD molecule pTau217, was tested using the self-developed and optimized nanoflow cytometry-based technology, which not only detected the positive ratio of EVs but also concurrently presented the corresponding particle size of the EVs, in discovery (n = 310) and validation (n = 213) cohorts. Plasma GABRD+- or GPR162+-carrying pTau217-EVs were significantly reduced in AD compared with healthy control (HC). Additionally, the size distribution of GABRD+- and GPR162+-carrying pTau217-EVs were significantly different between AD and non-AD dementia (NAD). An integrative model, combining age, the number and corresponding size of the distribution of GABRD+- or GPR162+-carrying pTau217-EVs, accurately and sensitively discriminated AD from HC [discovery cohort, area under the curve (AUC) = 0.96; validation cohort, AUC = 0.93] and effectively differentiated AD from NAD (discovery cohort, AUC = 0.91; validation cohort, AUC = 0.90). This study showed that brain regionally enriched neuronal EVs carrying pTau217 in plasma may serve as a robust diagnostic and differential diagnostic tool in both clinical practice and trials for AD. |
| first_indexed | 2024-03-07T14:36:07Z |
| format | Article |
| id | doaj.art-a7a95c4cbfa741f6bd4a0e024bcebc83 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-03-07T14:36:07Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-a7a95c4cbfa741f6bd4a0e024bcebc832024-03-05T20:40:46ZengBMCActa Neuropathologica Communications2051-59602024-03-0112111910.1186/s40478-024-01727-wBlood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosisZhen Guo0Chen Tian1Yang Shi2Xue-Ru Song3Wei Yin4Qing-Qing Tao5Jie Liu6Guo-Ping Peng7Zhi-Ying Wu8Yan-Jiang Wang9Zhen-Xin Zhang10Jing Zhang11Department of Pathology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Pathology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Pathology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Pathology, The First Affiliated Hospital, Zhejiang University School of MedicineCore Facilities, Zhejiang University School of MedicineDepartment of Neurology and Research Center of Neurology in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of MedicineDepartment of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurology and Research Center of Neurology in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of MedicineDepartment of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Clinical Epidemiology Unit, Peking Union Medical College Hospital, Chinese Academy of Medical SciencesDepartment of Pathology, The First Affiliated Hospital, Zhejiang University School of MedicineAbstract Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer’s disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD and GPR162 were identified as novel brain regionally enriched plasma EVs markers. The performance of GABRD and GPR162, along with the AD molecule pTau217, was tested using the self-developed and optimized nanoflow cytometry-based technology, which not only detected the positive ratio of EVs but also concurrently presented the corresponding particle size of the EVs, in discovery (n = 310) and validation (n = 213) cohorts. Plasma GABRD+- or GPR162+-carrying pTau217-EVs were significantly reduced in AD compared with healthy control (HC). Additionally, the size distribution of GABRD+- and GPR162+-carrying pTau217-EVs were significantly different between AD and non-AD dementia (NAD). An integrative model, combining age, the number and corresponding size of the distribution of GABRD+- or GPR162+-carrying pTau217-EVs, accurately and sensitively discriminated AD from HC [discovery cohort, area under the curve (AUC) = 0.96; validation cohort, AUC = 0.93] and effectively differentiated AD from NAD (discovery cohort, AUC = 0.91; validation cohort, AUC = 0.90). This study showed that brain regionally enriched neuronal EVs carrying pTau217 in plasma may serve as a robust diagnostic and differential diagnostic tool in both clinical practice and trials for AD.https://doi.org/10.1186/s40478-024-01727-wAlzheimer’s diseaseBlood-based biomarkerExtracellular vesiclesNanoflow cytometryBrain regionally enrichedDifferential diagnosis |
| spellingShingle | Zhen Guo Chen Tian Yang Shi Xue-Ru Song Wei Yin Qing-Qing Tao Jie Liu Guo-Ping Peng Zhi-Ying Wu Yan-Jiang Wang Zhen-Xin Zhang Jing Zhang Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis Acta Neuropathologica Communications Alzheimer’s disease Blood-based biomarker Extracellular vesicles Nanoflow cytometry Brain regionally enriched Differential diagnosis |
| title | Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis |
| title_full | Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis |
| title_fullStr | Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis |
| title_full_unstemmed | Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis |
| title_short | Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis |
| title_sort | blood based cns regionally and neuronally enriched extracellular vesicles carrying ptau217 for alzheimer s disease diagnosis and differential diagnosis |
| topic | Alzheimer’s disease Blood-based biomarker Extracellular vesicles Nanoflow cytometry Brain regionally enriched Differential diagnosis |
| url | https://doi.org/10.1186/s40478-024-01727-w |
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