Differential patterns of central synucleinopathy and catecholaminergic abnormalities in Lewy body diseases and multiple system atrophy.

INTRODUCTION

Parkinson's disease (PD), pure autonomic failure (PAF), and multiple system atrophy (MSA) feature intracellular deposition of alpha-synuclein and catecholamine deficiency in the putamen or heart. This retrospective, cross-sectional, observational study assessed relationships of cerebrospinal fluid alpha-synuclein seed amplification assay (CSF SAA) data with catecholamine deficiency indicated by positron emission tomography (PET).

METHODS

In groups with PD, PAF, parkinsonian MSA (MSA-P), or cerebellar MSA (MSA-C) SAAs were conducted by Rocky Mountain Laboratories (RML) and Amprion, Inc. using different assay conditions. 18F-DOPA PET examined putamen dopaminergic innervation, and 18F-dopamine PET assessed cardiac noradrenergic innervation.

RESULTS

CSF SAAs by both RML and Amprion separated PD or PAF from MSA. The Amprion assay detected type 1 seeding associated with Lewy body diseases (LBDs) in 22/24 (92%) PD patients and 15/16 (94%) PAF patients and type 2 seeding associated with MSA in 9/10 (90%) MSA-P and 3/4 (75%) MSA-C patients (p < 0.0001). All of 24 PD and all of 9 MSA-P patients had low putamen/occipital cortex ratios of 18F-DOPA-derived radioactivity, while 11/13 (85%) PAF patients and 4/4 (100%) MSA-C patients had normal ratios. Contingency analyses of CSF SAA and brain 18F-DOPA PET efficiently separated the 4 groups (p < 0.0001).

CONCLUSION

CSF SAAs and cardiac 18F-dopamine PET distinguish LBDs from MSA but not PAF from PD or MSA-P from MSA-C. 18F-DOPA PET separates PAF from PD and MSA-P from MSA-C. Combining biomarkers differentiates among these synucleinopathies.