Mitophagy alterations in Alzheimer's disease are associated with granulovacuolar degeneration and early tau pathology.
Alzheimers Dement
; 2020 Oct 08.
Article
in En
| MEDLINE
| ID: mdl-33090691
ABSTRACT
INTRODUCTION:
The cytoprotective PTEN-induced kinase 1 (PINK1)-parkin RBR E3 ubiquitin protein ligase (PRKN) pathway selectively labels damaged mitochondria with phosphorylated ubiquitin (pS65-Ub) for their autophagic removal (mitophagy). Because dysfunctions of mitochondria and degradation pathways are early features of Alzheimer's disease (AD), mitophagy impairments may contribute to the pathogenesis.METHODS:
Morphology, levels, and distribution of the mitophagy tag pS65-Ub were evaluated by biochemical analyses combined with tissue and single cell imaging in AD autopsy brain and in transgenic mouse models.RESULTS:
Analyses revealed significant increases of pS65-Ub levels in AD brain, which strongly correlated with granulovacuolar degeneration (GVD) and early phospho-tau deposits, but were independent of amyloid beta pathology. Single cell analyses revealed predominant co-localization of pS65-Ub with mitochondria, GVD bodies, and/or lysosomes depending on the brain region analyzed.DISCUSSION:
Our study highlights mitophagy alterations in AD that are associated with early tau pathology, and suggests that distinct mitochondrial, autophagic, and/or lysosomal failure may contribute to the selective vulnerability in disease.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Risk_factors_studies
Language:
En
Journal:
Alzheimers Dement
Year:
2020
Document type:
Article
Affiliation country:
Estados Unidos