This study explores the diagnostic potential of olfactory mucosa (OM) and blood samples for the identification of new and disease-specific peripheral biomarkers for α-synucleinopathies, in particular Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). By employing a multidisciplinary approach, we will investigate whether these biomarkers are already altered in subjects with isolated REM sleep behavior disorder (iRBD), a prodromal stage of α-synucleinopathies. A total of 66 subjects, including PD (n=18), DLB (n=15), iRBD (n=13) and healthy subjects (HS, n=20) were enrolled and underwent olfactory evaluation before OM and blood collection. Olfactory function was assessed using the Burghart Sniffin’ Sticks test. OM samples were collected separately from the left and right nostrils for comprehensive analysis. Seed amplification assay (SAA), Western blot, ELISA, ELLATM and MiSeq Illumina were employed. SAA is currently employed to determine αSynD distribution in OM and blood samples. Preliminary results suggest that the seeding activity in the OM is higher in iRBD subjects compared to PD and DLB, without correlation to olfactory impairment severity. The SAA protocol for blood analysis is still under optimization. Blood NfL levels are significantly elevated in iRBD, PD, and DLB compared to HS. Mild increases in blood α-synuclein levels are also observed in iRBD and PD patients. The blood levels of IL-9 are significantly lower in iRBD and PD patients compared to HS, while those of IL-1RA are significantly lower in DLB patients compared to HS. Higher levels of Actinobacteriota are present in the OM of iRBD subjects with respect to HS, with further studies underway. Our findings suggest that αSynD is detectable in the OM of iRBD subjects with greater efficiency than in PD and DLB, suggesting that iRBD subjects may represent a more severe form of α-synucleinopathy after phenoconversion. This multidisciplinary approach suggests that several biomarkers are already altered in iRBD subjects. Therefore, our approach might contribute to identify iRBD subjects at higher risk of progressing to α-synucleinopathies
Identification of early and peripheral biomarkers predictive of Parkinson’s disease and dementia with Lewy bodies / M.B. Bacinoglu, R. Domina, A. Lombardo, A. Ciullini, A. Consonni, E. Puleo, I. Linda Dellarole, M. Miglietti, S. Maria Silvia Portaleone, G. Bufano, F. Angelo Cazzaniga, F. Bellandi, A. Emanuele Elia, G. Didato, E. Salvi, P. Tiraboschi, F. Baggi, F. Moda. Protein misfolding and aggregation in disease Mantova 2025.
Identification of early and peripheral biomarkers predictive of Parkinson’s disease and dementia with Lewy bodies
M.B. Bacinoglu;F. Moda
2025
Abstract
This study explores the diagnostic potential of olfactory mucosa (OM) and blood samples for the identification of new and disease-specific peripheral biomarkers for α-synucleinopathies, in particular Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). By employing a multidisciplinary approach, we will investigate whether these biomarkers are already altered in subjects with isolated REM sleep behavior disorder (iRBD), a prodromal stage of α-synucleinopathies. A total of 66 subjects, including PD (n=18), DLB (n=15), iRBD (n=13) and healthy subjects (HS, n=20) were enrolled and underwent olfactory evaluation before OM and blood collection. Olfactory function was assessed using the Burghart Sniffin’ Sticks test. OM samples were collected separately from the left and right nostrils for comprehensive analysis. Seed amplification assay (SAA), Western blot, ELISA, ELLATM and MiSeq Illumina were employed. SAA is currently employed to determine αSynD distribution in OM and blood samples. Preliminary results suggest that the seeding activity in the OM is higher in iRBD subjects compared to PD and DLB, without correlation to olfactory impairment severity. The SAA protocol for blood analysis is still under optimization. Blood NfL levels are significantly elevated in iRBD, PD, and DLB compared to HS. Mild increases in blood α-synuclein levels are also observed in iRBD and PD patients. The blood levels of IL-9 are significantly lower in iRBD and PD patients compared to HS, while those of IL-1RA are significantly lower in DLB patients compared to HS. Higher levels of Actinobacteriota are present in the OM of iRBD subjects with respect to HS, with further studies underway. Our findings suggest that αSynD is detectable in the OM of iRBD subjects with greater efficiency than in PD and DLB, suggesting that iRBD subjects may represent a more severe form of α-synucleinopathy after phenoconversion. This multidisciplinary approach suggests that several biomarkers are already altered in iRBD subjects. Therefore, our approach might contribute to identify iRBD subjects at higher risk of progressing to α-synucleinopathies
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
