CNS tau efflux via exosomes is likely increased in Parkinson's disease but not in Alzheimer's disease
Open accessAbstract
Introduction: Alzheimer's disease (AD) and Parkinson's disease (PD) involve tau pathology. Tau is detectable in blood, but its clearance from neuronal cells and the brain is poorly understood. Methods: Tau efflux from the brain to the blood was evaluated by administering radioactively labeled and unlabeled tau intracerebroventricularly in wild‐type and tau knock‐out mice, respectively. Central nervous system (CNS)–derived tau in L1CAM‐containing exosomes was further characterized extensively in human plasma, including by single molecule array technology with 303 subjects. Results: The efflux of Tau, including a fraction via CNS‐derived L1CAM exosomes, was observed in mice. In human plasma, tau was explicitly identified within L1CAM exosomes. In contrast to AD patients, L1CAM exosomal tau was significantly higher in PD patients than controls and correlated with cerebrospinal fluid tau. Conclusions: Tau is readily transported from the brain to the blood. The mechanisms of CNS tau efflux are likely different between AD and PD.
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The rationale for using plasma biomarkers as proxies for brain processes has been demonstrated for multiple neurodegenerative diseases.
“The rationale for using plasma biomarkers as proxies for brain processes [173] has been demonstrated for multiple neurodegenerative diseases [174, 175].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [175]
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- Authors
- Shi, M., Kovac, A., Korff, A., Cook, T. J., Ginghina, C., Bullock, K. M., Yang, L., Stewart, T., Zheng, D., Aro, P., Atik, A., Kerr, K. F., Zabetian, C. P., Peskind, E. R., Hu, S., Quinn, J. F., Galasko, D. R., Montine, T. J., Banks, W. A., & Zhang, J.
- Affiliations
- University of Washington (US)
- Geriatric Research, Education, and Clinical Center Veterans Affairs Puget Sound Health Care System Seattle WA USA
- Department of Pathology University of Washington School of Medicine Seattle WA USA
- Oregon Health & Science University (US)
- University of California San Diego (US)
- Corresponding author
- Zhang, Jing
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-05-24
- Volume
- 12
- Issue
- 11
- Pages
- 1125-1131
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC5107127
- OpenAlex
- W2398356848
- Cited by
- 206
- References
- 29
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 29 · 2023: 27 · 2022: 29 · 2021: 24 · 2020: 31 · 2019: 16 · 2018: 17 · 2017: 6 · 2016: 4
- FWCI
- 11.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (U01 NS082137, P30 ES007033‐6364, R01 AG033398, R01 ES016873, R01 ES019277, R01 NS057567, P50 NS062684‐6221, R21 NS085425, R01 NS065070, P50 AG05131)
- Alzheimer's Association (2015‐NIRG‐342009)
- U.S. Department of Veterans Affairs
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau protein
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Biological Transport, Blood-Brain Barrier, Female, Humans, Male, Mice, Inbred C57BL, Middle Aged, Parkinson Disease, tau Proteins, Mice, Knockout, Neural Cell Adhesion Molecule L1, Exosomes
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