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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

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 Borberg^1,2,3, Zoe Swank^1,2,3, Tal Gilboa^1,2,3

¹Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States.

Medrxiv : the Preprint Server for Health Sciences

|November 24, 2025

Summary

This summary is machine-generated.

Researchers developed a digital Seed Amplification Assay (dSAA) to precisely quantify TDP-43 seeds in cerebrospinal fluid (CSF). This sensitive diagnostic tool shows potential for identifying frontotemporal dementia with TDP-43 pathology (FTLD-TDP) and related diseases.

Keywords:

Cerebrospinal fluid Frontotemporal lobar dementia Seed amplification assay TDP-43

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Published on: February 12, 2015

Area of Science:

Neuroscience
Biochemistry
Medical Diagnostics

Background:

Dementia is often caused by misfolded protein aggregates.
Distinct dementia subtypes share symptoms, complicating diagnosis without biomarkers.
Misdiagnosis in clinical trials hinders effective drug development for dementia.

Purpose of the Study:

To develop a precise method for quantifying TDP-43 seeds in cerebrospinal fluid (CSF).
To establish a sensitive diagnostic tool for frontotemporal dementia with TDP-43 pathology (FTLD-TDP).

Main Methods:

Developed a digital Seed Amplification Assay (dSAA).
dSAA isolates individual protein aggregates in nanoliter compartments for quantification.
Assayed TDP-43 seeds in CSF samples from FTLD-TDP patients and healthy controls.

Main Results:

Elevated TDP-43 seed concentrations were detected in FTLD-TDP patients.
Seed concentrations correlated with disease severity.
Demonstrated dSAA's potential as a sensitive diagnostic tool.

Conclusions:

Introduced a novel quantitative, high-sensitivity digital assay for TDP-43 seeds in CSF.
The assay offers single-aggregate resolution and a low limit of detection (LOD).
Established a foundation for diagnostic and monitoring tools for FTLD-TDP and other TDP-43 proteinopathies.