title: CNS tau efflux via exosomes is likely increased in Parkinson's disease but not in Alzheimer's disease.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Tau is readily transported from the brain to the blood. The mechanisms of CNS tau efflux are likely different between AD and PD.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Andrej
authors.initials: A
authors.lastname: Kovac
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Ane
authors.initials: A
authors.lastname: Korff
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Cook
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ginghina
authors.affiliation: 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.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Bullock
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Tessandra
authors.initials: T
authors.lastname: Stewart
authors.affiliation: 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.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aro
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Anzari
authors.initials: A
authors.lastname: Atik
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kerr
authors.affiliation: 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.
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
authors.affiliation: 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.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.affiliation: 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.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Hu
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.affiliation: Department of Neurosciences and Shiley-Marcos Alzheimer's Disease Research Center, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Galasko
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.affiliation: 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.
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; C558298:Mapt protein, mouse; D039842:Neural Cell Adhesion Molecule L1; D016875:tau Proteins
keywords: Alzheimer's disease; Biomarkers; Blood plasma; Central nervous system protein efflux; Central nervous system-derived exosomes; Parkinson's disease; Tau