Quantifying Iron, Protein Deposits, and Myelin Integrity in Parkinson’s Disease and Multiple System Atrophy

Motivation: The neurodegenerative patterns of Parkinson's disease (PD) and multiple system atrophy (MSA) remain to be explored. Goal(s): To investigate the nigrostriatal iron, α-synuclein deposition, and white matter myelin integrity in the PD and MSA. Approach: DECOMPOSE-QSM was applied in 184 old normal controls (ONC), 321 PD, and 22 MSA patients to quantify nigrostriatal iron, α-synuclein content, and white matter myelin content. Results: PD and MSA show caudate protein and nigral iron deposition; putamen iron deposition is unique to MSA. The corticospinal tract was demyelinated in PD, while some accompanying fibers showed compensatory myelination. MSA exhibits compensatory myelination in cerebellar pathways. Impact: This study clarifies distinct neurodegenerative patterns in PD and MSA, highlighting specific iron and protein deposition and myelin integrity alterations, potentially aiding targeted diagnostics and treatments of synucleinopathies.