Affiliations: [a] Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| [b] Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA
| [c]
Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovak Republic | [d] Department of Pharmacology and Toxicology, The University of Veterinary Medicine and Pharmacy, Kosice, Slovak Republic | [e] AXON Neuroscience SE, Bratislava, Slovak Republic | [f] Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA
| [g] Department of Pathology, Peking University Health Science Center and Peking University Third Hospital, Beijing, China
Correspondence:
[*]
Correspondence to: William A. Banks, VAPSHCS, 1660S. Columbian Way, Seattle, WA 98108, USA. Tel.: +1 206 764
2701; Fax: +1 206764 2569; E-mail: wabanks1@uw.edu.
Abstract: Tauopathies are a hallmark of many neurodegenerative diseases, including Alzheimer’s disease and traumatic brain injuries. It has been demonstrated that amyloid-beta peptides, alpha-synuclein, and prion proteins cross the blood-brain barrier (BBB), contributing to their abilities to induce disease. Very little is known about whether tau proteins can cross the BBB. Here we systematically characterized several key forms of tau proteins to cross the BBB, including Tau-441 (2N4R), Tau-410 (2N3R), truncated tau 151–391 (0N4R), and truncated tau 121–227. All of these tau proteins crossed the BBB readily and bidirectonally; however, only Tau-410 had a saturable component to its influx. The tau proteins also entered the blood after their injection into the brain, with Tau 121–227 having the slowest exit from brain. The tau proteins varied in regards to their enzymatic stability in brain and blood and in their peripheral pharmacokinetics. These results show that blood-borne tau proteins could contribute to brain tauopathies. The result also suggest that the CNS can contribute to blood levels of tau, raising the possibility that, as suggested for other misfolded proteins, blood levels of tau proteins could be used as a biomarker of CNS disease.
Keywords: Alzheimer’s disease, blood-brain barrier, tau protein, tauopathy
