AI Article Synopsis

  • - Idiopathic Parkinson's disease (iPD) has varying causes, but researchers have identified two specific subtypes based on the severity of neuronal respiratory complex I (CI) deficiency.
  • - The CI deficient (CI-PD) subtype, which makes up about 25% of iPD cases, shows widespread CI deficiency and is linked to non-tremor dominant symptoms, along with distinct gene expression and more mitochondrial DNA damage.
  • - In contrast, the non-CI deficient (nCI-PD) subtype does not show significant mitochondrial issues outside a specific brain region and is more likely to present with tremor dominant symptoms, offering insights for better understanding and treatment of iPD.

Article 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11059185PMC
http://dx.doi.org/10.1038/s41467-024-47867-4DOI Listing

Publication Analysis

Top Keywords

complex deficiency
8
idiopathic parkinson's
8
parkinson's disease
8
disease subtypes
8
mitochondrial complex
4
deficiency stratifies
4
stratifies idiopathic
4
disease
4
disease idiopathic
4
disease ipd
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!