Multiple system atrophy (MSA) is a rare and rapidly progressive neurodegenerative disorder characterized by a variable combination of autonomic failure, parkinsonism, and cerebellar ataxia, with a median survival of 8-10 years from symptom onset. Its aetiology remains poorly understood, as most cases are sporadic and environmental contributors remain unclear. Neuropathologically, MSA is defined by the accumulation of α-synuclein within oligodendroglial cells, forming glial cytoplasmic inclusions that drive widespread neurodegeneration in striatonigral and olivopontocerebellar systems. Recent advances in diagnostic criteria and biomarker development have improved disease recognition; however, early diagnosis remains challenging, particularly during the prodromal phase, when clinical features overlap with other α-synucleinopathies. Advances in fluid biomarkers and multimodal imaging are expected to facilitate earlier detection, improve diagnostic accuracy, and provide more robust tools for monitoring disease progression. Therapeutic development has largely focused on targeting α-synuclein pathology, but these approaches have not yet demonstrated consistent clinical benefit, highlighting the biological complexity of MSA. In the absence of curative treatments, management remains largely supportive, aimed at symptom control, particularly addressing autonomic dysfunction and motor impairment. Emerging care models, including telemedicine and multidisciplinary management, are reshaping clinical practice and may improve access to specialized care. Bridging advances in pathophysiology with patient-centred care will be essential for improving outcomes in MSA.
J. Buonocore, Bianca Calió, Fabian Leys et al.· Journal of neural transmissi...· 0 citations
Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder, yet it remains unclear whether cortical architecture can reveal biologically distinct subtypes with distinct molecular and serum biomarker signatures. Two hundred PD patients and 121 healthy controls underwent structural MRI. Subject-specific cortical similarity networks were constructed using Morphometric INverse Divergence (MIND), and subtypes were identified with HYDRA. Spatial patterns were linked to regional gene expression from the Allen Human Brain Atlas through partial least squares regression, followed by functional and cell-type enrichment analyses. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified using single-molecule array assays. No significant MIND differences emerged when PD patients were analysed as a single group. HYDRA identified two subtypes (ARI = 0.85) with divergent cortical organization that only partially overlapped with conventional motor phenotypes. Cluster 1 exhibited temporo-parietal MIND increases associated with synaptic and oligodendroglial signatures, without serum biomarker associations. Cluster 2 showed widespread fronto-cingulate MIND reductions enriched for mitochondrial, lysosomal, and proteostatic pathways, including the KEGG Parkinson’s disease pathway, and these reductions correlated with higher serum NfL and GFAP. These findings reveal two biologically distinct PD subtypes with divergent molecular architecture and systemic neurodegeneration beyond conventional motor phenotyping.
M. Bianco, Camilla Calomino, Maria Celeste Bonacci et al.· International Journal of Mol...· 0 citations