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Updated: Jan 10, 2026
A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Digital seed amplification assay for TDP-43 aggregate quantification in CSF
Ella Borberg1,2,3, Zoe Swank1,2,3, Tal Gilboa1,2,3
1Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States.
Introduction:
Dementia is commonly caused by underlying pathologies driven by misfolded protein aggregates. Although dementia subtypes have distinct mechanisms, overlapping symptoms make diagnosis without biomarkers difficult. Misdiagnosis has previously hindered drug development by enrolling patients non-specifically in trials.
Methods:
We developed a digital Seed amplification assay (dSAA) that isolates individual aggregates in nanoliter compartments, enabling precise quantification of TDP-43 seeds in cerebrospinal fluid (CSF).
Results:
Testing 40 CSF samples from patients with genetic and sporadic FTLD-TDP, as well as healthy controls, we found elevated seed concentrations in FTLD-TDP patients that correlated with disease severity, demonstrating the potential of dSAA as a sensitive diagnostic tool.
Discussion:
This study demonstrates a new quantitative, high-sensitivity digital assay for TDP-43 seeds in CSF. The platform's single-aggregate resolution and low LOD establish a technical foundation for developing a diagnostic and monitoring tool for FTLD-TDP and other TDP-43-related diseases.
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