Neuroinflammation and Mitochondrial Dysfunction in Parkinson's Disease: Connecting Neuroimaging with Pathophysiology

There is a pressing need for disease-modifying therapies in patients suffering from neurodegenerative diseases, including Parkinson's disease (PD). However, these disorders face unique challenges in clinical trial designs to assess the neuroprotective properties of potential drug candidates. One of these challenges relates to the often unknown individual disease mechanisms that would, however, be relevant for targeted treatment strategies. Neuroinflammation and mitochondrial dysfunction are two proposed pathophysiological hallmarks and are considered to be highly interconnected in PD. Innovative neuroimaging methods can potentially help to gain deeper insights into one's predominant disease mechanisms, can facilitate patient stratification in clinical trials, and could potentially map treatment responses. This review aims to highlight the role of neuroinflammation and mitochondrial dysfunction in patients with PD (PwPD). We will specifically introduce different neuroimaging modalities, their respective technical hurdles and challenges, and their implementation into clinical practice. We will gather preliminary evidence for their potential use in PD research and discuss opportunities for future clinical trials.

Automated summary

There is a need for disease-modifying therapies for neurodegenerative diseases such as Parkinson's disease (PD). However, clinical trial designs for these disorders face challenges in assessing the neuroprotective properties of potential drugs due to unknown individual disease mechanisms. Neuroimaging methods can provide insights into disease mechanisms, help with patient stratification, and map treatment responses. This review highlights the role of neuroinflammation and mitochondrial dysfunction in PD, discusses different neuroimaging modalities and their challenges, and explores opportunities for future clinical trials.