Objective: To investigate substantia nigra pars compacta (SNc) area together with dopaminergic neuron count and density in atypical parkinsonisms in relation to Parkinson’s disease (PD) and clinical characteristics.

Background: SNc plays a key role in regulating movements. In PD, the primary loss of dopaminergic neurons occurs in the SNc, but nonmotor symptoms may be related to neuronal changes in other brain regions [1]. However, there are limited data on how SNc neurons evolve in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). In the present ongoing study, we are collecting clinicopathological details of PD, MSA and PSP patients and comparing the conditions with each other in relation to neuronal structures and clinical characteristics.

Method: Postmortem neuropathological autopsy samples and clinical data were collected from 58 patients in Turku University Hospital, Finland. The study included 41 patients with neuropathologically confirmed PD, 8 patients with PSP and 9 with MSA. Tyrosine hydroxylase (TH) -positive neuron numbers in the SNc were calculated and neuron densities measured together with SNc area. The values were corrected with the Abercrombie method as described previously [2]. The Kruskal-Wallis test was used for statistical comparisons between groups with appropriate corrections for multiple comparisons.

Results: SNc TH-positive neuron density did not differ between PD, PSP and MSA patients (p=0.26, Kruskal-Wallis). Patients with PD had a higher SNc neuron count (p=0.03) and larger SNc area (p=0.004) than patients with MSA. There were no significant differences in SNc neuron counts or areas between PD and PSP patients. Age at death was lower in PSP (mean = 71.4 years [SD=7.4]) and MSA (mean = 64.7 [SD=9.7]) patients as compared to PD patients (mean = 79.7 [SD=7.0]) (p<0.001).

Conclusion: These preliminary results suggest that SNc neuron count and area are reduced in MSA compared to PD, but there are no similar differences between PD and PSP. Importantly, dopaminergic neuron density seems to remain unaltered in both MSA and PSP compared to PD. Further analyses will be performed when a larger number of postmortem PSP and MSA patients becomes available.

References: [1] Langston JW. Ann Neurol. 2006 Apr;59(4):591-6.
[2] Saari L, et al. Ann Neurol. 2021 May;89(5):1046-1050.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/substantia-nigra-dopaminergic-neuron-density-in-pd-psp-and-msa-an-interim-clinicopathological-analysis/