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

doi: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

Alzheimers Dement. 2016 Nov;12(11):1125-1131. doi: 10.1016/j.jalz.2016.04.003. Epub 2016 May 24.

Authors

Min Shi¹, Andrej Kovac², Ane Korff¹, Travis J Cook¹, Carmen Ginghina¹, Kristin M Bullock³, Li Yang¹, Tessandra Stewart¹, Danfeng Zheng⁴, Patrick Aro¹, Anzari Atik¹, Kathleen F Kerr⁵, Cyrus P Zabetian⁶, Elaine R Peskind⁷, Shu-Ching Hu⁶, Joseph F Quinn⁸, Douglas R Galasko⁹, Thomas J Montine¹, William A Banks³, Jing Zhang¹⁰

Affiliations

¹ Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
² Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA; Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
³ Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
⁴ Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA; Department of Pathology, Peking University Health Science Center and Peking University Third Hospital, Beijing, China.
⁵ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁶ Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Parkinson's Disease Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
⁷ Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA; Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
⁸ Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
⁹ Department of Neurosciences and Shiley-Marcos Alzheimer's Disease Research Center, University of California at San Diego, La Jolla, CA, USA.
¹⁰ Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA; Department of Pathology, Peking University Health Science Center and Peking University Third Hospital, Beijing, China. Electronic address: zhangj@uw.edu.

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.

Keywords: Alzheimer's disease; Biomarkers; Blood plasma; Central nervous system protein efflux; Central nervous system-derived exosomes; Parkinson's disease; Tau.

Publication types

Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Aged
Aged, 80 and over
Alzheimer Disease / metabolism*
Animals
Biological Transport / physiology
Blood-Brain Barrier / metabolism
Exosomes / metabolism*
Female
Humans
Male
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Neural Cell Adhesion Molecule L1 / metabolism
Parkinson Disease / metabolism*
tau Proteins / genetics
tau Proteins / metabolism*

Substances

MAPT protein, human
Mapt protein, mouse
Neural Cell Adhesion Molecule L1
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding