Percorrer por autor "Fasano, Alfonso"
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- Disease modification in advanced parkinson’s disease: a review and roadmap for paving the way for next-generation interventionsPublication . Groppa, Sergiu; Fasano, Alfonso; Urso, Daniele; Yang, Xinjie; Popescu, Bogdan; Klivenyi, Peter; Laar, Teus van; Jost, Wolfgang; Garcia-Ruiz, Pedro J.; Bhidayasiri, Roongroj; Outeiro, TiagoParkinson’s disease (PD) exhibits highly heterogeneous clinical trajectories, yet “advanced PD” (aPD) lacks a standardized definition. Current reliance on clinical milestones (e.g., motor fluctuations, cognitive decline) is limited by non-linear progression and the absence of objective measures. Although biomarkers like aggregated α-synuclein, MRI, and PET are under investigation, their correlation with clinical progression remains modest. Robust, reproducible endpoints are urgently needed to evaluate disease-modifying therapies across diverse phenotypes, accounting for genetic background, age of onset, co-pathologies, and motor/autonomic/cognitive domains. Given this complexity, single-target interventions are likely insufficient. We propose a multi-domain therapeutic framework for aPD that integrates: (A) simultaneous targeting of key pathological cascades, including α-synuclein aggregation, mitochondrial dysfunction, oxidative stress, proteostasis imbalance, neuroinflammation, and the gut–brain axis; (B) biology-driven patient stratification using emerging biomarkers to match subgroups with targeted interventions; and (C) systematic management of comorbidities and lifestyle factors, such as cardiovascular health and exercise, to enhance neuroresilience. Finally, advancing aPD care requires addressing systemic determinants, including global healthcare inequities, and prioritizing caregiver well-being. Mechanistically informed, patient-centered strategies that combine multi-target therapies with precision stratification and holistic support will be essential to modify disease progression and improve long-term outcomes.
- Neuroimaging and pathology biomarkers in parkinson’s disease and parkinsonismPublication . Cilia, Roberto; Arnaldi, Dario; Ballanger, Bénédicte; Ceravolo, Roberto; Micco, Rosa De; Del Sole, Angelo; Eleopra, Roberto; Endo, Hironobu; Fasano, Alfonso; Hoenig, Merle C.; Horsager, Jacob; Lehéricy, Stéphane; Leta, Valentina; Moda, Fabio; Nolano, Maria; Outeiro, Tiago; Parkkinen, Laura; Pavese, Nicola; Quattrone, Andrea; Ray, Nicola J.; Reich, Martin M.; Rektorová, Irena; Strafella, Antonio P.; Tagliavini, Fabrizio; Tessitore, Alessandro; van Eimeren, ThiloThe “Neuroimaging and Pathology Biomarkers in Parkinson’s Disease” course held on 12–13 September 2025 in Milan, Italy, convened an international faculty to review state-ofthe- art biomarkers spanning neurotransmitter dysfunction, protein pathology and clinical translation. Here, we synthesize the four themed sessions and highlights convergent messages for diagnosis, stratification and trial design. The first session focused on neuroimaging markers of neurotransmitter dysfunction, highlighting how positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) provided complementary insights into dopaminergic, noradrenergic, cholinergic and serotonergic dysfunction. The second session addressed in vivo imaging of protein pathology, presenting recent advances in PET ligands targeting α- synuclein, progress in four-repeat tau imaging for progressive supranuclear palsy and corticobasal syndromes, and the prognostic relevance of amyloid imaging in the context of mixed pathologies. Imaging of neuroinflammation captures inflammatory processes in vivo and helps study pathophysiological effects. The third session bridged pathology and disease mechanisms, covering the biology of α-synuclein and emerging therapeutic strategies, the clinical potential of seed amplification assays and skin biopsy, the impact of co-pathologies on disease expression, and the “brain-first” versus “body-first” model of pathological spread. Finally, the fourth session addressed disease progression and clinical translation, focusing on imaging predictors of phenoconversion from prodromal to clinically overt stages of synucleinopathies, concepts of neural reserve and compensation, imaging correlates of cognitive impairment, and MRI approaches for atypical parkinsonism. Biomarker-informed pharmacological, infusion-based, and surgical strategies, including network-guided and adaptive deep brain stimulation, were discussed as examples of how multimodal biomarkers may inform personalized management. Across all sessions, the need for harmonization, longitudinal validation, and pathology-confirmed outcome measures was consistently emphasized as essential for advancing biomarker qualification in multicentre research and clinical practice.