Mitochondrial complex I deficiency stratifies idiopathic Parkinson's disease.
Nat Commun
; 15(1): 3631, 2024 Apr 29.
Article
in En
| MEDLINE
| ID: mdl-38684731
ABSTRACT
Idiopathic Parkinson's disease (iPD) is believed to have a heterogeneous pathophysiology, but molecular disease subtypes have not been identified. Here, we show that iPD can be stratified according to the severity of neuronal respiratory complex I (CI) deficiency, and identify two emerging disease subtypes with distinct molecular and clinical profiles. The CI deficient (CI-PD) subtype accounts for approximately a fourth of all cases, and is characterized by anatomically widespread neuronal CI deficiency, a distinct cell type-specific gene expression profile, increased load of neuronal mtDNA deletions, and a predilection for non-tremor dominant motor phenotypes. In contrast, the non-CI deficient (nCI-PD) subtype exhibits no evidence of mitochondrial impairment outside the dopaminergic substantia nigra and has a predilection for a tremor dominant phenotype. These findings constitute a step towards resolving the biological heterogeneity of iPD with implications for both mechanistic understanding and treatment strategies.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Parkinson Disease
/
DNA, Mitochondrial
/
Mitochondrial Diseases
/
Electron Transport Complex I
/
Mitochondria
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Document type:
Article
Affiliation country:
Norway