Illustration of misfolded proteins in a brain, representing the detection of vCJD prions.

Decoding the Tricky Variant: A New Test for Creutzfeldt-Jakob Disease

Kai Mendoza in Health & Wellness December 2025 • 4 min read.

"A breakthrough in diagnosing a rare form of Creutzfeldt-Jakob disease could help prevent future outbreaks and protect vulnerable populations."

Variant Creutzfeldt-Jakob disease (vCJD) is a rare and fatal brain disorder linked to the consumption of meat from cattle infected with bovine spongiform encephalopathy (BSE), commonly known as mad cow disease. Most cases have occurred in the United Kingdom, raising concerns about potential asymptomatic carriers within the population.

Until recently, all confirmed vCJD cases involved individuals with a specific genetic makeup (methionine homozygous) at codon 129 of the prion protein gene. However, the emergence of a patient with a different genetic variation (methionine/valine heterozygous) in 2016 raised concerns about a possible 'second wave' of vCJD, as this patient's symptoms mimicked those of sporadic CJD (sCJD), making diagnosis challenging.

To address this diagnostic challenge, researchers have developed a highly sensitive and specific test based on protein misfolding cyclic amplification (PMCA). This test can detect vCJD prions in cerebrospinal fluid (CSF), even in individuals with the methionine/valine heterozygous variation, allowing for accurate differentiation between vCJD and sCJD.

Unlocking the PMCA Test: How It Works and What It Reveals

Illustration of misfolded proteins in a brain, representing the detection of vCJD prions.

The newly developed test utilizes a technique called protein misfolding cyclic amplification (PMCA). PMCA works by amplifying misfolded prion proteins, which are the hallmark of vCJD. The test is performed on cerebrospinal fluid (CSF) samples, which are obtained through a spinal tap.

The process involves:

Seeding: A small amount of the patient's CSF, potentially containing misfolded prions, is added to a solution containing normal prion proteins.
Amplification: The mixture undergoes repeated cycles of incubation and sonication (ultrasound). The misfolded prions act as 'seeds', converting the normal prion proteins into the misfolded form.
Detection: After several cycles, the amplified misfolded prions are detected using Western blotting, a technique that identifies specific proteins.

The test's high sensitivity and specificity allows it to accurately detect vCJD prions, even when they are present in very low concentrations. This is particularly important for diagnosing vCJD in individuals with the methionine/valine heterozygous variation, as their symptoms can be less distinct.

Why This Matters: Implications for Public Health and Future Research

The development of this highly specific PMCA test represents a significant advancement in the diagnosis and management of vCJD. It enables clinicians to accurately differentiate between vCJD and sCJD, even in patients with atypical genetic profiles, leading to earlier and more appropriate treatment.

Furthermore, the test has important implications for public health. By identifying individuals with vCJD, including those who may be asymptomatic carriers, it can help prevent further transmission of the disease through blood transfusions or surgical procedures.

Future research should focus on further refining the PMCA test and exploring its potential for diagnosing other prion diseases. The test could also be used to monitor the effectiveness of therapeutic interventions and to identify individuals at high risk of developing vCJD.

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: 10.3201/eid2407.172105, Alternate LINK

Title: Diagnosis Of Methionine/Valine Variant Creutzfeldt-Jakob Disease By Protein Misfolding Cyclic Amplification

Subject: Infectious Diseases

Journal: Emerging Infectious Diseases

Publisher: Centers for Disease Control and Prevention (CDC)

Authors: Daisy Bougard, Maxime Bélondrade, Charly Mayran, Lilian Bruyère-Ostells, Sylvain Lehmann, Chantal Fournier-Wirth, Richard S. Knight, Robert G. Will, Alison J.E. Green

Published: 2018-07-01

Everything You Need To Know

What is variant Creutzfeldt-Jakob disease (vCJD)?

Variant Creutzfeldt-Jakob disease (vCJD) is a rare and fatal brain disorder linked to the consumption of meat from cattle infected with bovine spongiform encephalopathy (BSE), often called mad cow disease. Most cases have occurred in the United Kingdom. This disease is characterized by the misfolding of prion proteins, leading to brain damage.

How does the new test for vCJD work?

The newly developed test is based on protein misfolding cyclic amplification (PMCA). This technique amplifies misfolded prion proteins found in the cerebrospinal fluid (CSF). The process involves seeding the CSF sample with normal prion proteins, amplifying the misfolded prions through repeated cycles of incubation and sonication, and finally detecting the amplified prions using Western blotting. This method allows for the detection of vCJD prions even in very low concentrations.

Why is this new test for vCJD so important?

This test is crucial because it enables the accurate differentiation between vCJD and sporadic CJD (sCJD). This is particularly important in patients with the methionine/valine heterozygous variation, as their symptoms can be less distinct, making diagnosis challenging. The test's high sensitivity ensures that vCJD can be detected earlier, allowing for better patient management and potentially preventing the spread of the disease. This advancement is significant for public health and future research.

What is the significance of the genetic makeup at codon 129 of the prion protein gene in vCJD?

The genetic makeup at codon 129 of the prion protein gene is significant because it influences susceptibility to vCJD. Until recently, all confirmed vCJD cases involved individuals with a specific genetic makeup (methionine homozygous). The emergence of a patient with a different genetic variation (methionine/valine heterozygous) raised concerns about a possible 'second wave' of vCJD, as this patient's symptoms mimicked those of sporadic CJD (sCJD). This genetic variation complicates diagnosis and underscores the importance of the new PMCA test.

What are the implications of this new test?

The implications of the new PMCA test are significant for public health and future research. Earlier and more accurate diagnosis of vCJD allows for better patient management and can help prevent potential outbreaks. The ability to detect vCJD in individuals with atypical genetic profiles, such as the methionine/valine heterozygous variation, is a major breakthrough. This advancement represents a significant step forward in understanding and combating this deadly disease.