Open AccessPeri‐arterial pathways for clearance of α‐Synuclein and tau from the brain: Implications for the pathogenesis of dementias and for immunotherapy
Author(s) -
Nimmo Jacqui,
Johnston David A.,
Dodart J. C.,
MacGregorSharp Matthew T.,
Weller Roy O.,
Nicoll James A. R.,
Verma Ajay,
Carare Roxana O.
Publication year - 2020
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1002/dad2.12070
Subject(s) - pathogenesis , tauopathy , immunolabeling , pathology , hippocampus , immunotherapy , medicine , neuroscience , biology , disease , immunology , immunohistochemistry , immune system , neurodegeneration
Accumulation of amyloid beta (Aβ), α‐synuclein (αSyn), and tau in dementias indicates their age‐related failure of elimination from the brain. Aβ is eliminated along basement membranes in walls of cerebral arterioles and leptomeningeal arteries (intramural peri‐arterial drainage [IPAD]); IPAD is impaired with age. We test the hypothesis that αSyn and tau are also eliminated from the normal brain along IPAD pathways. Methods Soluble αSyn or tau was injected into mouse hippocampus. Animals were perfused 5 minutes to 7 days post‐injection. Blood vessels were identified by ROX‐SE for light‐sheet and immunolabeling for confocal microscopy. IPAD was quantified by measuring the proportion of arterioles with αSyn/tau. Results αSyn and tau are eliminated from the brain by IPAD but with different dynamics. Discussion Age‐related failure of IPAD may play a role in the pathogenesis of synucleinopathies and tauopathies. αSyn persists within IPAD at 24 hours, which may affect immunotherapy for αSyn.