Digital seed amplification assay for TDP-43 aggregate quantification in CSF.

ABSTRACT:

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

SUBMITTER: Borberg E 

PROVIDER: S-EPMC12633125 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature