Biomarkers

Area of Science:

• Neuroscience
• Biochemistry
• Biomarker Discovery

Background:

• Plasma assays offer minimally invasive biomarkers for neurodegenerative diseases.
• The Nucleic acid Linked Immuno-Sandwich Assay (NULISA) platform was used to quantify 123 plasma proteins.
• The study included over 3,000 individuals with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), Parkinson's disease (PD), and controls.

Purpose of the Study:

• To identify general and disease-specific plasma protein biomarkers for neurodegeneration.
• To evaluate the performance of the NULISA platform in quantifying these biomarkers.
• To correlate plasma protein levels with established neuroimaging and fluid biomarkers.

Main Methods:

• Quantification of 123 plasma proteins in 3,668 samples using NULISA.
• Differential abundance, ROC, and AUC analyses were performed for AD, DLB, FTD, and PD.
• Analyses included correlations with amyloid PET, tau PET, CSF Aβ42/Aβ40, and CDR scores.

Main Results:

• 78 proteins associated with AD, 2 with DLB, 2 with FTD, and 1 with PD.
• Plasma pTau217 showed high accuracy (AUC 0.81 for AD, 0.95 for amyloid positivity).
• High concordance (93.59%) between plasma pTau217 and Centiloid levels was achieved.

Conclusions:

• NULISA is a reliable platform for quantifying plasma proteins in neurodegenerative diseases.
• Plasma pTau217 is a validated predictive biomarker for AD, correlating strongly with neuroimaging markers.
• These findings support NULISA's potential for research and clinical applications in neurodegenerative disease diagnostics.