Seed-competent high-molecular-weight tau species accumulates in the cerebrospinal fluid of Alzheimer's disease mouse model and human patients.

Autor:	Takeda S; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA. takeda@cgt.med.osaka-u.ac.jp., Commins C; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., DeVos SL; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., Nobuhara CK; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., Wegmann S; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., Roe AD; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., Costantino I; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., Fan Z; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., Nicholls SB; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., Sherman AE; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., Trisini Lipsanopoulos AT; Ann Romney Center for Neurological Diseases, Brigham and Women's Hospital, Boston, MA., Scherzer CR; Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham & Women's Hospital, Cambridge, MA., Carlson GA; McLaughlin Research Institute, Great Falls, MT., Pitstick R; McLaughlin Research Institute, Great Falls, MT., Peskind ER; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA.; Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA., Raskind MA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA.; Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA., Li G; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA.; Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA., Montine TJ; Department of Pathology, University of Washington School of Medicine, Seattle, WA., Frosch MP; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., Hyman BT; Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA.
Jazyk:	angličtina
Zdroj:	Annals of neurology [Ann Neurol] 2016 Sep; Vol. 80 (3), pp. 355-67. Date of Electronic Publication: 2016 Aug 03.
DOI:	10.1002/ana.24716
Abstrakt:	Objective: Cerebrospinal fluid (CSF) tau is an excellent surrogate marker for assessing neuropathological changes that occur in Alzheimer's disease (AD) patients. However, whether the elevated tau in AD CSF is just a marker of neurodegeneration or, in fact, a part of the disease process is uncertain. Moreover, it is unknown how CSF tau relates to the recently described soluble high-molecular-weight (HMW) species that is found in the postmortem AD brain and can be taken up by neurons and seed aggregates. Methods: We have examined seeding and uptake properties of brain extracellular tau from various sources, including interstitial fluid (ISF) and CSF from an AD transgenic mouse model and postmortem ventricular and antemortem lumbar CSF from AD patients. Results: We found that brain ISF and CSF tau from the AD mouse model can be taken up by cells and induce intracellular aggregates. Ventricular CSF from AD patients contained a rare HMW tau species that exerted a higher seeding activity. Notably, the HMW tau species was also detected in lumbar CSF from AD patients, and its levels were significantly elevated compared to control subjects. HMW tau derived from CSF of AD patients was seed competent in vitro. Interpretation: These findings suggest that CSF from an AD brain contains potentially bioactive HMW tau species, giving new insights into the role of CSF tau and biomarker development for AD. Ann Neurol 2016;80:355-367. Competing Interests: We have no potential conflicts. (© 2016 American Neurological Association.)
Databáze:	MEDLINE
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