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 Quinn, Douglas R. Galasko, Thomas J. Montine, William A. Banks, Jing Zhang

Research output: Contribution to journalArticle

35 Citations (Scopus)

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

Fingerprint

Neural Cell Adhesion Molecule L1
Exosomes
Parkinson Disease
Alzheimer Disease
Central Nervous System
Brain
Knockout Mice
Cerebrospinal Fluid
Pathology
Technology

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
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Shi, M., Kovac, A., Korff, A., Cook, T. J., Ginghina, C., Bullock, K. M., ... 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

CNS tau efflux via exosomes is likely increased in Parkinson's disease but not in Alzheimer's disease. / Shi, Min; Kovac, Andrej; Korff, Ane; Cook, Travis J.; Ginghina, Carmen; Bullock, Kristin M.; Yang, Li; Stewart, Tessandra; Zheng, Danfeng; Aro, Patrick; Atik, Anzari; Kerr, Kathleen F.; Zabetian, Cyrus P.; Peskind, Elaine R.; Hu, Shu Ching; Quinn, Joseph; Galasko, Douglas R.; Montine, Thomas J.; Banks, William A.; Zhang, Jing.

In: Alzheimer's and Dementia, Vol. 12, No. 11, 01.11.2016, p. 1125-1131.

Research output: Contribution to journalArticle

Shi, M, Kovac, A, Korff, A, Cook, TJ, Ginghina, C, Bullock, KM, Yang, L, Stewart, T, Zheng, D, Aro, P, Atik, A, Kerr, KF, Zabetian, CP, Peskind, ER, Hu, SC, Quinn, J, Galasko, DR, Montine, TJ, Banks, WA & 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, vol. 12, no. 11, pp. 1125-1131. https://doi.org/10.1016/j.jalz.2016.04.003
Shi, Min ; Kovac, Andrej ; Korff, Ane ; Cook, Travis J. ; Ginghina, Carmen ; Bullock, Kristin M. ; Yang, Li ; Stewart, Tessandra ; Zheng, Danfeng ; Aro, Patrick ; Atik, Anzari ; Kerr, Kathleen F. ; Zabetian, Cyrus P. ; Peskind, Elaine R. ; Hu, Shu Ching ; Quinn, Joseph ; Galasko, Douglas R. ; Montine, Thomas J. ; Banks, William A. ; Zhang, Jing. / CNS tau efflux via exosomes is likely increased in Parkinson's disease but not in Alzheimer's disease. In: Alzheimer's and Dementia. 2016 ; Vol. 12, No. 11. pp. 1125-1131.
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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.",
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AU - Ginghina, Carmen

AU - Bullock, Kristin M.

AU - Yang, Li

AU - Stewart, Tessandra

AU - Zheng, Danfeng

AU - Aro, Patrick

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AU - Kerr, Kathleen F.

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AU - Peskind, Elaine R.

AU - Hu, Shu Ching

AU - Quinn, Joseph

AU - Galasko, Douglas R.

AU - Montine, Thomas J.

AU - Banks, William A.

AU - Zhang, Jing

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N2 - 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.

AB - 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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