The Target48 Neurodegeneration Panel: A Novel Tool for Profiling Protein Signatures in Neurodegenerative Disorders

Introduction: Novel tools for absolute quantification of established and emerging fluid neuro-biomarkers are required to advance diagnostic studies and improve biological insights. Methods: We conducted an extensive analytical and clinical validation of the Olink Target 48 Neurodegeneration panel (T48 Neuropanel) in 352 paired CSF and plasma samples from cognitively unimpaired controls (CU), Alzheimer dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), n=44 per group. Comparisons with benchmark assays were performed. Results: Good detectability (CSF: 31 out of 42 assays; plasma: 38 out of 42 assays) and technical performance was observed. Benchmark assays showed good correlations, supporting method transformation formulas. Next to emerging biomarkers (MMP10, ITGB2), discriminative performance was excellent in AD: CSF pTau217: AUC=1; FTD: plasma NfL: AUC=0.952; and DLB: CSF DDC: AUC=0.901. Discussion: This analytical and clinical validation of the T48 Neuropanel highlights initial cut-offs and emerging biomarkers to aid clinical studies for the diagnosis, prognosis, and monitoring of neurodegenerative diseases. Highlights: The T48 Neuropanel shows robust analytical performance, with high detectability across both plasma and CSF matrices. The T48 Neuropanel validates established (i.e., pTau217, Abeta42, NfL, and GFAP) and emerging biomarkers (i.e., DDC, MMP10, ITGB2, ITGAM, NPTX2, NPTXR, SMOC1, sTREM1, and sTREM2) in CSF and plasma. CSF NfL, GFAP, ITGB2, and ITGAM and plasma GFAP were dysregulated across AD, FTD, and DLB dementias. -The multiplex design of the T48 Neuropanel enables rich biological interpretation by simultaneously quantifying established and emerging neurodegeneration biomarkers. Importantly, the inclusion of absolute quantification facilitates the establishment of cut-offs, supporting its potential for clinical translation.