Surreal illustration of biomarkers in cerebrospinal fluid within a brain.

Prion Diseases: New Biomarkers Offer Hope for Early Detection and Treatment

Beau Callahan in Health & Wellness June 2025 • 4 min read.

"Discover how cutting-edge research into fluid biomarkers is revolutionizing the diagnosis and management of human prion diseases, potentially leading to earlier interventions and improved clinical trial outcomes."

Human prion diseases are a group of rare and devastating neurodegenerative conditions characterized by the misfolding of the prion protein. These diseases, which include sporadic Creutzfeldt-Jakob disease (sCJD), variant Creutzfeldt-Jakob disease (vCJD), and inherited prion diseases (IPD), pose significant diagnostic and therapeutic challenges. The rapid progression and varied clinical presentations of prion diseases often lead to delayed diagnosis, hindering timely intervention.

Recent advances in biomarker research offer a beacon of hope for improving the diagnosis and management of prion diseases. Fluid biomarkers, such as those found in cerebrospinal fluid (CSF) and blood, are showing promise in detecting early signs of prion-related changes in the brain. These biomarkers not only aid in diagnosis but also hold potential for predicting disease progression, stratifying patients for clinical trials, and assessing the risk of developing prion disease in asymptomatic individuals.

This article explores the current state of fluid biomarker research in human prion diseases, highlighting key findings, clinical applications, and future directions. We will delve into the various types of biomarkers, their diagnostic accuracy, and their potential to transform the landscape of prion disease management.

The Promise of Fluid Biomarkers in Prion Disease

Surreal illustration of biomarkers in cerebrospinal fluid within a brain.

Fluid biomarkers are revolutionizing the approach to diagnosing and managing prion diseases. Traditional diagnostic methods often rely on clinical symptoms, imaging techniques, and tissue biopsies, which can be invasive and may not provide definitive results in the early stages of the disease. Fluid biomarkers, on the other hand, offer a less invasive and more accessible means of detecting prion-related changes in the body.

Cerebrospinal fluid (CSF) has long been a primary source of biomarkers for prion diseases. Several surrogate markers in CSF have been identified, reflecting the rapid neurodegeneration characteristic of these conditions. These markers include:

14-3-3 proteins: These proteins are released into the CSF as a result of neuronal damage. While not specific to prion diseases, their presence can indicate rapid neurodegeneration.
Tau protein: Total tau concentration in CSF increases with neuronal damage. High levels of tau can be indicative of rapidly progressive sCJD.
Neurofilament light chain (NfL): NfL is a neuronal cytoskeleton component released during neuronal damage. Elevated levels in CSF suggest neurodegeneration and can be useful in atypical cases.
Alpha-synuclein: This protein appears to be a surrogate marker for neuronal damage in prion disease and has shown remarkable diagnostic value.

In addition to surrogate markers, the real-time quaking-induced conversion (RT-QuIC) assay has emerged as a highly sensitive and specific diagnostic tool. RT-QuIC detects the seeding activity of abnormal prion protein in CSF, providing a direct measure of prion disease pathology. This assay has become a cornerstone of prion disease diagnosis at referral and surveillance centers.

Future Directions

The field of prion disease biomarker research is rapidly evolving, with ongoing efforts to improve diagnostic accuracy, identify novel biomarkers, and develop therapeutic strategies. Future research directions include exploring the potential of blood-based biomarkers for early detection and screening, developing quantitative RT-QuIC assays to assess disease severity, and investigating the role of biomarkers in predicting treatment response. By continuing to advance our understanding of prion diseases and leveraging the power of fluid biomarkers, we can pave the way for earlier diagnosis, improved patient care, and ultimately, effective treatments for these devastating conditions.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.mcn.2018.12.003, Alternate LINK

Title: Review: Fluid Biomarkers In The Human Prion Diseases

Subject: Cell Biology

Journal: Molecular and Cellular Neuroscience

Publisher: Elsevier BV

Authors: Andrew G.B. Thompson, Simon H. Mead

Published: 2019-06-01

Everything You Need To Know

How are prion diseases currently diagnosed, and what role do fluid biomarkers play in improving this process?

Prion diseases, such as sporadic Creutzfeldt-Jakob disease (sCJD), variant Creutzfeldt-Jakob disease (vCJD), and inherited prion diseases (IPD), are diagnosed using a combination of clinical evaluation, imaging techniques, and laboratory tests. Recent advances focus on fluid biomarkers found in cerebrospinal fluid (CSF) and blood. These biomarkers include surrogate markers like 14-3-3 proteins, Tau protein, Neurofilament light chain (NfL), and Alpha-synuclein, which indicate neuronal damage. The real-time quaking-induced conversion (RT-QuIC) assay is also used to detect abnormal prion protein. These methods aid in earlier and more accurate diagnosis, addressing the challenges posed by the varied clinical presentations and rapid progression of these conditions.

In what ways are fluid biomarkers transforming the approach to detecting and managing prion diseases?

Fluid biomarkers are revolutionizing the detection and management of prion diseases by providing a less invasive means of detecting prion-related changes in the body. Traditional methods often involve invasive procedures like tissue biopsies, which may not be definitive in early stages. Fluid biomarkers, found in cerebrospinal fluid (CSF) and blood, offer a more accessible way to identify early signs of prion diseases. Surrogate markers like 14-3-3 proteins, Tau protein, Neurofilament light chain (NfL), and Alpha-synuclein in CSF can indicate neuronal damage. The real-time quaking-induced conversion (RT-QuIC) assay directly measures abnormal prion protein, enhancing diagnostic accuracy and enabling earlier intervention.

Why is cerebrospinal fluid (CSF) considered a primary source of biomarkers in the diagnosis of prion diseases, and what specific markers are analyzed?

Cerebrospinal fluid (CSF) plays a crucial role in prion disease diagnosis due to the presence of several key biomarkers. These include 14-3-3 proteins, which indicate rapid neurodegeneration; Tau protein, with high levels suggesting rapidly progressive sCJD; Neurofilament light chain (NfL), useful in atypical cases of neurodegeneration; and Alpha-synuclein, a surrogate marker for neuronal damage. Additionally, the real-time quaking-induced conversion (RT-QuIC) assay, which detects the seeding activity of abnormal prion protein, has become a cornerstone in prion disease diagnosis. While blood-based biomarkers are being explored, CSF remains central to current diagnostic practices.

What makes the real-time quaking-induced conversion (RT-QuIC) assay a significant advancement in prion disease diagnostics compared to traditional surrogate markers?

The real-time quaking-induced conversion (RT-QuIC) assay is significant because it directly detects the seeding activity of abnormal prion protein in cerebrospinal fluid (CSF). Unlike surrogate markers such as 14-3-3 proteins, Tau protein, Neurofilament light chain (NfL) and Alpha-synuclein, which only indicate neuronal damage, RT-QuIC provides a direct measure of prion disease pathology. This makes it a highly sensitive and specific diagnostic tool, now considered a cornerstone of prion disease diagnosis at referral and surveillance centers. Its ability to detect the abnormal prion protein early enhances the accuracy and speed of diagnosis, improving patient management.

What are the future directions of prion disease biomarker research, and how might these advancements impact the diagnosis and treatment of these conditions?

Future research in prion disease biomarker development aims to improve diagnostic accuracy, discover new biomarkers, and create therapeutic strategies. Key areas include exploring blood-based biomarkers for early detection and screening, which would offer a less invasive alternative to cerebrospinal fluid (CSF) analysis. Another focus is developing quantitative RT-QuIC assays to assess disease severity and monitor treatment response. Researchers are also investigating the role of biomarkers in predicting how patients will respond to potential treatments. These advancements could lead to earlier diagnosis, more effective patient care, and the development of targeted therapies for these devastating conditions.