# Neuroimaging and Pathology Biomarkers in Parkinson’s Disease and Parkinsonism

## TL;DR

This paper summarizes a conference on biomarkers for Parkinson’s disease and related conditions, focusing on neuroimaging and protein pathology to improve diagnosis and treatment.

## Contribution

The paper provides a synthesis of recent advances in neuroimaging and pathology biomarkers for Parkinson’s disease and parkinsonism, emphasizing their clinical translation.

## Key findings

- Neuroimaging techniques like PET and MRI offer insights into neurotransmitter dysfunction in Parkinson’s disease.
- In vivo imaging of protein pathology, such as α-synuclein and tau, is advancing diagnostic and prognostic capabilities.
- Multimodal biomarkers can inform personalized treatment strategies, including deep brain stimulation.

## Abstract

The “Neuroimaging and Pathology Biomarkers in Parkinson’s Disease” course held on 12–13 September 2025 in Milan, Italy, convened an international faculty to review state-of-the-art biomarkers spanning neurotransmitter dysfunction, protein pathology and clinical translation. Here, we synthesize the four themed sessions and highlights convergent messages for diagnosis, stratification and trial design. The first session focused on neuroimaging markers of neurotransmitter dysfunction, highlighting how positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) provided complementary insights into dopaminergic, noradrenergic, cholinergic and serotonergic dysfunction. The second session addressed in vivo imaging of protein pathology, presenting recent advances in PET ligands targeting α-synuclein, progress in four-repeat tau imaging for progressive supranuclear palsy and corticobasal syndromes, and the prognostic relevance of amyloid imaging in the context of mixed pathologies. Imaging of neuroinflammation captures inflammatory processes in vivo and helps study pathophysiological effects. The third session bridged pathology and disease mechanisms, covering the biology of α-synuclein and emerging therapeutic strategies, the clinical potential of seed amplification assays and skin biopsy, the impact of co-pathologies on disease expression, and the “brain-first” versus “body-first” model of pathological spread. Finally, the fourth session addressed disease progression and clinical translation, focusing on imaging predictors of phenoconversion from prodromal to clinically overt stages of synucleinopathies, concepts of neural reserve and compensation, imaging correlates of cognitive impairment, and MRI approaches for atypical parkinsonism. Biomarker-informed pharmacological, infusion-based, and surgical strategies, including network-guided and adaptive deep brain stimulation, were discussed as examples of how multimodal biomarkers may inform personalized management. Across all sessions, the need for harmonization, longitudinal validation, and pathology-confirmed outcome measures was consistently emphasized as essential for advancing biomarker qualification in multicentre research and clinical practice.