Category: Parkinsonism, Atypical: MSA
Objective: To investigate deeply-phenotyped cohorts of parkinsonian syndromes using proteomic technologies for identification of biomarkers for differential diagnosis
Background: Proteomic technologies like Olink® Explore 3072 (Olink® 3k) and SomaScan®, are increasingly used for in vivo biomarker discovery. However, large-scale proteomic investigations of atypical parkinsonian syndromes are often limited by small cohort sizes and ante mortem diagnostic inaccuracies. Deeply phenotyping cohorts to maximize antemortem diagnostic certainty helps to create clean cohorts, less prone to noise created by misdiagnosis.
Method: We deeply phenotyped a cohort of 15 patients suffering from Parkinson’s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and healthy controls (HC), respectively. Deep phenotyping of PD, MSA and PSP comprised detailed clinical assessments, MRI imaging and a combination of CSF a-synuclein seeding amplification assays (SAA), FDG-PET, Tau-PET, Deprenyl-PET (astrogliosis) and TSPO-PET imaging (microglial activation). After deep phenotyping, CSF samples (total n = 60) were analyzed in parallel on the Olink® 3k and SomaScan® platform, allowing for detection of up to 2953 and 7596 proteins, respectively. Multiple-group comparison followed by FDR correction was used to identify potential biomarkers for differential diagnosis between cohorts.
Results: A total of 1594 and 7521 proteins were detectable in CSF samples using the Olink®3k and SomaScan® platform, respectively. Of these, 296 and 220 proteins were statistically significant different between groups (p < 0.05), of which 8 and 3 proteins remained statistically significant after FDR correction for multiple testing (p < 0.05). On both platforms, neurofilament light chain (NfL) was amongst these key hits, showing higher values in MSA and PSP compared to PD.
Conclusion: Deep phenotyping of study cohorts enables large scale proteomic approaches even in small cohorts. Interestingly, NfL, a known marker for neuroaxonal damage which has already been shown to be upregulated in MSA and PSP compared to PD using targeted quantitative immunoassays, remained one of the key hits for biomarkers of differential diagnosis in this large-scale proteomic approach. Combining our proteomic data with previous immunoassay studies strongly supports NfL to be included as biomarker in the diagnostic workup of parkinsonian syndromes.
To cite this abstract in AMA style:S. Katzdobler, A. Bernhardt, G. Nübling, C. Palleis, U. Fietzek, E. Weidinger, M. Brendel, G. Höglinger, J. Levin. In vivo proteomic investigation of deeply phenotyped parkinsonian syndromes for biomarkers of differential diagnosis [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/in-vivo-proteomic-investigation-of-deeply-phenotyped-parkinsonian-syndromes-for-biomarkers-of-differential-diagnosis/. Accessed September 22, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/in-vivo-proteomic-investigation-of-deeply-phenotyped-parkinsonian-syndromes-for-biomarkers-of-differential-diagnosis/