CNS tau efflux via exosomes is likely increased in Parkinson's disease but not in Alzheimer's disease

Min Shi, Andrej Kovac, Ane Korff, Travis J. Cook, Carmen Ginghina, Kristin M. Bullock, Li Yang, Tessandra Stewart, Danfeng Zheng, Patrick Aro, Anzari Atik, Kathleen F. Kerr, Cyrus P. Zabetian, Elaine R. Peskind, Shu Ching Hu, Joseph F. Quinn, Douglas R. Galasko, Thomas J. Montine, William A. Banks, Jing Zhang

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1125-1131
Number of pages7
JournalAlzheimer's and Dementia
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2016

Keywords

  • Alzheimer's disease
  • Biomarkers
  • Blood plasma
  • Central nervous system protein efflux
  • Central nervous system-derived exosomes
  • Parkinson's disease
  • Tau

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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  • Cite this

    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. C., Quinn, J. F., Galasko, D. R., Montine, T. J., Banks, W. A., & Zhang, J. (2016). CNS tau efflux via exosomes is likely increased in Parkinson's disease but not in Alzheimer's disease. Alzheimer's and Dementia, 12(11), 1125-1131. https://doi.org/10.1016/j.jalz.2016.04.003