Mitochondrial complex I deficiency stratifies idiopathic Parkinson's disease.
Nat Commun
; 15(1): 3631, 2024 Apr 29.
Article
en 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.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Enfermedad de Parkinson
/
ADN Mitocondrial
/
Enfermedades Mitocondriales
/
Complejo I de Transporte de Electrón
/
Mitocondrias
Límite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Nat Commun
/
Nature communications
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Noruega