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

• Published in: Alzheimer's & dementia Vol. 12; no. 11; pp. 1125 - 1131
• Main Authors: 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 F, Galasko, Douglas R, Montine, Thomas J, Banks, William A, Zhang, Jing
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2016
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer's disease; Animals; Biological Transport - physiology; Biomarkers; Blood plasma; Blood-Brain Barrier - metabolism; Central nervous system protein efflux; Central nervous system-derived exosomes; Exosomes - metabolism; Female; Humans; Male; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Neural Cell Adhesion Molecule L1 - metabolism; Neurology; Parkinson Disease - metabolism; Parkinson's disease; Tau; tau Proteins - genetics; tau Proteins - metabolism; Parkinson's disease; Central nervous system protein efflux; Central nervous system-derived exosomes; Biomarkers; Tau; Alzheimer's disease; Blood plasma
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1016/j.jalz.2016.04.003

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.