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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
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Proteopathic Seed Amplification Assays for Neurodegenerative Disorders
Natália do Carmo Ferreira1, Byron Caughey1
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA.
Clinics in Laboratory Medicine
|July 29, 2020
Summary
New ultrasensitive assays detect protein aggregates in neurodegenerative diseases like Parkinson's and Alzheimer's. These prion-like seeding assays offer accurate diagnosis and potential for new therapeutic development.
Area of Science:
- Biochemistry
- Neurology
- Biomarker Discovery
Background:
- Neurodegenerative diseases are often characterized by protein aggregation.
- There is a critical need for early diagnostic biomarkers for these debilitating conditions.
- Prion-like seeding capacity of aggregated proteins offers a novel target for diagnostic assays.
Purpose of the Study:
- To develop and evaluate ultrasensitive assays for detecting protein aggregates in neurodegenerative diseases.
- To explore the diagnostic potential of prion-like seeding assays for conditions such as Creutzfeldt-Jakob disease, synucleinopathies, and tauopathies.
- To assess the utility of these assays in improving diagnostics and guiding therapeutic development.
Main Methods:
- Development of ultrasensitive cellular and cell-free assays.
- Utilizing the prion-like seeding capacity of protein aggregates.
- Application of prion RT-QuIC, biosensor cell, and tau RT-QuIC assays.
- Testing assays with cerebrospinal fluid and nasal brushings.
Main Results:
- Prion RT-QuIC assays enable accurate antemortem diagnosis of Creutzfeldt-Jakob disease.
- Synucleinopathy assays demonstrate high diagnostic sensitivity for Parkinson disease and dementia with Lewy bodies using cerebrospinal fluid.
- Tau RT-QuIC assays can detect and differentiate tau aggregates in various tauopathies, including Alzheimer disease and frontotemporal degeneration.
Conclusions:
- Expanding the panel of seed amplification assays holds significant promise for improving the diagnosis of neurodegenerative proteinopathies.
- These ultrasensitive assays represent a major advancement in biomarker discovery for neurological disorders.
- Further development and application of these assays are expected to accelerate the development of targeted therapeutics.

