Peri-arterial pathways for clearance of α-Synuclein and tau from the brain: Implications for the pathogenesis of dementias and for immunotherapy.
Alzheimers Dement (Amst)
; 12(1): e12070, 2020.
Article
in En
| MEDLINE
| ID: mdl-32782922
ABSTRACT
INTRODUCTION:
Accumulation of amyloid beta (Aß), α-synuclein (αSyn), and tau in dementias indicates their age-related failure of elimination from the brain. Aß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Etiology_studies
Language:
En
Journal:
Alzheimers Dement (Amst)
Year:
2020
Document type:
Article