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CSF Test Distinguishes Prion Disease from Other Causes of Rapidly Progressive Dementia

By LabMedica International staff writers
Posted on 11 Mar 2025

Rapidly progressive dementias are a category of dementia where patients experience a swift decline from the onset of symptoms to losing functional independence, typically within two years. More...

During the early stages of these dementias, patients often present with nonspecific symptoms that make it difficult to pinpoint a clear diagnosis. However, it is essential to quickly identify the exact cause, as some forms, particularly those caused by autoimmune processes, can be treated, while others cannot. One such form is human prion disease, or Creutzfeldt-Jakob disease (CJD), which is caused by the misfolding of a normal prion protein—an essential protein found in everyone’s body. This misfolding can occur due to genetic mutations that make the protein prone to misfolding, or from spontaneous folding errors. The misfolded protein can then induce other correctly folded prion proteins to adopt the abnormal form, starting a chain reaction. Over time, this process leads to the destruction of neurons. Unfortunately, no cure currently exists for CJD.

Until recently, lab tests for CJD were limited to general markers of neuronal degeneration. These tests could detect the rapid destruction of brain tissue but could not definitively identify the cause. Now, researchers at Mayo Clinic (Rochester, MN, USA) have developed an advanced test that can differentiate prion diseases from other types of rapidly progressive dementias. This new test, conducted using cerebrospinal fluid (CSF), enables quick and accurate diagnoses, which is critical for identifying treatable autoimmune dementias and improving patient care. The RT-QuIC Prion test for CSF can distinguish prion disease from other rapidly progressive dementias, including autoimmune dementias and fast-progressing Alzheimer’s disease. The test provides patients with a clear diagnosis of rapidly progressive dementia faster, thanks to its high sensitivity.

The RT-QuIC (real-time quaking-induced conversion) assay marks the first time clinicians can obtain a specific diagnostic result for prion disease with very high accuracy. Before this test, the cause of the disease could only be conclusively determined after an autopsy. RT-QuIC for prion disease is the only antemortem clinical test of its kind, which does not require a brain biopsy. The RT-QuIC test has been shown to be highly sensitive using CSF samples, which are low-risk and can be handled in a standard clinical laboratory operating at biosafety level 2 (BSL-2). Now, patients with rapidly progressive dementias can receive a definitive diagnosis quickly, with results available in less than a week, a remarkable achievement considering the specialized nature of the RT-QuIC test.

“Basically, you take the patient’s CSF, mix it with a recombinant substrate prion protein that was made in-house at Mayo Clinic, and a fluorescent dye that labels the protein aggregates generated in the reaction,” said Jack Wu, Ph.D., a clinical chemistry fellow who developed and validated the test. “You incubate this plate at a temperature of 55 degrees Celsius while shaking it with certain reagents. It measures for the fluorescence every 45 minutes and does this for 36 hours. The most critical component of this test is the production of high-quality substrate proteins, which sets the basis for the assay’s superior performance in detecting some rare subtypes of human prion diseases.”

Related Links:
Mayo Clinic


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