Mitochondrial DNA copy number in neurodegenerative diseases: a global meta-analysis of 156 comparisons across 76 studies

The study analyzed 156 comparisons across 76 studies investigating mitochondrial DNA copy number (mtDNA-CN) in relation to neurodegenerative diseases. Mitochondria play a crucial role in cellular metabolism and dysfunction is linked to various chronic conditions, from cancer to obesity. While mtDNA-CN is being considered as a biomarker for neurodegenerative diseases, its relationship with neurodegeneration remains contentious.

The analysis revealed that overall, mtDNA-CN did not differ significantly across populations with or without neurodegenerative diseases. However, the heterogeneity among studies was extremely high (I2 = 99.5%), indicating that individual studies produced vastly different results. The type of diagnosed disease significantly influenced the variation in findings. For instance, Alzheimer's patients exhibited a 21% decrease in mtDNA-CN, whereas no change was observed in Parkinson's disease.

Moreover, the extent of mtDNA-CN reduction during neurodegeneration was more pronounced in older age groups. The tissue sampled for mtDNA-CN analysis did not consistently affect the results, with some exceptions related to specific diseases. Additionally, studies conducted in earlier years reported more substantial decreases in mtDNA-CN with neurodegeneration.

The study also noted that the general perception of decreased mtDNA-CN in neurodegenerative diseases is an oversimplification, likely stemming from the legacy effects of early research. Despite this, the analysis suggests that mtDNA levels could serve as valuable biomarkers for neurodegeneration, other diseases, and overall health metrics, provided that appropriate complications are taken into account.