Parkinson's disease is associated with clonal hematopoiesis with TET2 mutation

Area of Science:

• Hematology
• Neuroscience
• Immunology

Background:

• Clonal hematopoiesis of indeterminate potential (CHIP) involves premalignant expansion of mutated hematopoietic stem cells and is associated with immune alterations.
• Neuroinflammation and immune dysfunction are implicated in the pathophysiology of Parkinson's disease (PD).

Purpose of the Study:

• To investigate the potential association between CHIP and Parkinson's disease.
• To explore if CHIP prevalence differs in PD patients compared to controls and patients with isolated REM sleep behavior disorder (iRBD).

Main Methods:

• Targeted sequencing of 24 genes related to hematologic neoplasms was performed on peripheral blood DNA from 341 PD patients, 92 iRBD patients, and 5003 controls.
• PD cases were categorized by motor progression speed (fast, slow, typical).
• Multivariable logistic regression models assessed CHIP prevalence (≥1.0% variant allele fraction) against controls.

Main Results:

• CHIP, specifically with TET2 mutations, was more prevalent in PD patients than in controls (aOR 1.75, p=0.017).
• This association was particularly strong in the fast motor progression PD subgroup (aOR 3.19, p=0.004).
• No significant association was found between CHIP and iRBD.

Conclusions:

• Parkinson's disease is associated with increased odds of CHIP carrying TET2 mutations.
• The findings suggest a potential role for immune dysregulation in the underlying mechanisms of PD.
• CHIP may serve as a biomarker or contributor to PD pathogenesis, especially in rapidly progressing cases.