This new paper provides evidence of the interaction between iron accumulation and non-dopamine neurotransmitters in the pathogenesis of MSA and PD.

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  Multiple system atrophy (MSA) and Parkinson's disease (PD) exhibited distinct patterns of iron deposition in cortical and subcortical regions.

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  The cortical topography of susceptibility alterations in MSA and PD correlated to reference maps of cholinergic, noradrenaline, glutamate, serotonin, cannabinoids, and opioid systems.
  
  

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  The susceptibility-neurotransmitter correlation provided indicators for monitoring disease severity in MSA and PD.

  
  
  Neurobiol Dis

  
  

  . 2024 Jun 1:106549.

  doi: 10.1016/j.nbd.2024.106549. Online ahead of print.

  Quantitative susceptibility mapping of multiple system atrophy and Parkinson's disease correlates with neurotransmitter reference maps

  Su Yan ¹, Jun Lu ², Bingfang Duan ¹, Hongquan Zhu ¹, Dong Liu ¹, Li Li ¹, Yuanyuan Qin ¹, Yuanhao Li ³, Wenzhen Zhu ⁴

  Affiliations expand

  • PMID: 38830476
• DOI: 10.1016/j.nbd.2024.106549

Abstract

Background: Multiple system atrophy (MSA) and Parkinson's disease (PD) are neurodegenerative disorders characterized by α-synuclein pathology, disrupted iron homeostasis and impaired neurochemical transmission. Considering the critical role of iron in neurotransmitter synthesis and transport, our study aims to identify distinct patterns of whole-brain iron accumulation in MSA and PD, and to elucidate the corresponding neurochemical substrates.

Methods: A total of 122 PD patients, 58 MSA patients and 78 age-, sex-matched health controls underwent multi-echo gradient echo sequences and neurological evaluations. We conducted voxel-wise and regional analyses using quantitative susceptibility mapping to explore MSA or PD-specific alterations in cortical and subcortical iron concentrations. Spatial correlation approaches were employed to examine the topographical alignment of cortical iron accumulation patterns with normative atlases of neurotransmitter receptor and transporter densities. Furthermore, we assessed the associations between the colocalization strength of neurochemical systems and disease severity.

Results: MSA patients exhibited increased susceptibility in the striatal, midbrain, cerebellar nuclei, as well as the frontal, temporal, occipital lobes, and anterior cingulate gyrus. In contrast, PD patients displayed elevated iron levels in the left inferior occipital gyrus, precentral gyrus, and substantia nigra. The excessive iron accumulation in MSA or PD correlated with the spatial distribution of cholinergic, noradrenaline, glutamate, serotonin, cannabinoids, and opioid neurotransmitters, and the degree of this alignment was related to motor deficits.

Conclusions: Our findings provide evidence of the interaction between iron accumulation and non-dopamine neurotransmitters in the pathogenesis of MSA and PD, which inspire research on potential targets for pharmacotherapy.