Category: Parkinson's disease: Neuroimaging
Objective: To investigate the specific pathological changes in the substantia nigra (SN) across Parkinson’s disease (PD) subtypes, focusing on iron deposition and NM depletion both at baseline and longitudinally.
Background: Spatial patterns of brain atrophy in PD can be categorized into three subtypes: S1 (neocortical), S2 (limbic), and S3 (brainstem), identified by the Subtype and Stage Inference (SuStaIn) algorithm. While these subtypes describe brain atrophy, the detailed progression of SN pathology remains to be determined.
Method: We included 59 healthy controls (HC) and 206 PD patients categorized at baseline (Y0) into S0 (non-atrophy) (n=76), S1 (n=61), S2 (n=48), and S3 (n=21). Multimodal MRI, including NM-MRI and QSM(Quantitative Susceptibility Mapping) with chi-separation algorithm, was performed. Longitudinal analysis was conducted on a follow-up cohort (S0=13, S1=12, S2=20, S3=3). Voxel-wise analysis was performed using FSL-randomise with Threshold-Free Cluster Enhancement (TFCE), corrected for FWE (p < 0.05).
Results: At baseline (Y0), all PD subtypes showed a significant reduction of CNR (contrast-to-noise ratio) referenced to pons measured by NM-MRI and increased paramagnetic susceptibility in the SN compared to HC. Comparisons across subtypes revealed that S3 exhibited the highest iron deposition compared to S1 and S2. Conversely, S2 showed relatively preserved CNR compared to S1 and S3. Longitudinal analysis after 2 years revealed distinct progression patterns: S0 showed a significant increase in iron deposition in the anterior SN compared to S1 and S2. In contrast, S2 exhibited a decline in CNR compared to S3, despite its relative preservation at baseline.
Conclusion: The substantia nigra exhibits distinct pathological trajectories depending on the SuStaIn-defined subtype. Moreover, these findings reveal that the longitudinal course of substantia nigra pathology is highly divergent across PD subtypes. Such heterogeneity suggests that the progression of SN degeneration is intrinsically linked to the subtypes.
References: 1. Y. Sakato, A. Shima, Y. Terada, K. Takeda, H. Sakamaki-Tsukita, A. Nishida, K. Yoshimura, I. Wada, K. Furukawa, D. Kambe, H. Togo, Y. Mukai, M. Sawamura, E. Nakanishi, H. Yamakado, Y. Fushimi, T. Okada, Y. Takahashi, Y. Nakamoto, R. Takahashi, T. Hanakawa, N. Sawamoto, Delineating three distinct spatiotemporal patterns of brain atrophy in Parkinson’s disease. Brain 147, 3702–3713 (2024).
2. K. Furukawa, A. Shima, D. Kambe, A. Nishida, I. Wada, H. Sakamaki, K. Yoshimura, Y. Terada, Y. Sakato, M. Mitsuhashi, M. Sawamura, E. Nakanishi, Y. Taruno, H. Yamakado, Y. Fushimi, T. Okada, Y. Nakamoto, R. Takahashi, N. Sawamoto, Motor Progression and Nigrostriatal Neurodegeneration in Parkinson Disease. Ann. Neurol. 92, 110–121 (2022).
3. H.-G. Shin, J. Lee, Y. H. Yun, S. H. Yoo, J. Jang, S.-H. Oh, Y. Nam, S. Jung, S. Kim, M. Fukunaga, W. Kim, H. J. Choi, J. Lee, χ-separation: Magnetic susceptibility source separation toward iron and myelin mapping in the brain. Neuroimage 240, 118371 (2021).
To cite this abstract in AMA style:
A. Shima, Y. Sakato, R. Sakai, Y. Terada, D. Kambe, A. Nishida, K. Yoshimura, H. Sakamaki, I. Wada, M. Sawamura, E. Nakanishi, H. Yamakado, S. Okuchi, T. Okada, Y. Fushimi, Y. Nakamoto, R. Takahashi, R. Matsumoto, N. Sawamoto. Subtype-specific alterations of iron deposition and neuromelanin loss in the substantia nigra of Parkinson’s disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/subtype-specific-alterations-of-iron-deposition-and-neuromelanin-loss-in-the-substantia-nigra-of-parkinsons-disease/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/subtype-specific-alterations-of-iron-deposition-and-neuromelanin-loss-in-the-substantia-nigra-of-parkinsons-disease/