The early signs of Creutzfeldt-Jakob disease (CJD)—a rare, incurable brain disorder caused by infectious, misshapen proteins called prions—are difficult to interpret. At first, people may simply feel depressed and can undergo personality changes or bouts of psychosis. By the time memory failure, blindness, and coma set in, typically within a year of infection, death is usually imminent. Now, researchers report that a simple nasal swab may help physicians detect the disease far more accurately and earlier than current methods.

Finding simple, noninvasive diagnostic tests is “one of the holy grails” for CJD and other prion diseases, says biochemist Byron Caughey of the National Institute of Allergy and Infectious Diseases’ Rocky Mountain Laboratories in Hamilton, Montana, who helped lead the new work. Although there’s no cure for CJD, early diagnosis is important because it can help rule out other, treatable disorders, and it allows medical personnel to take precautions that prevent the disease from spreading to others through exposure to brain tissue or spinal fluid, he says. A type of the disease called variant CJD in humans results from eating meat infected with mad cow disease.

Researchers made a major stride toward better diagnostic methods in 2010, when Caughey and other researchers first described a new technique called the RT-QuIC test. The test requires removing cerebrospinal fluid (CSF) from patients by means of a spinal tap, putting samples into a bath of normally shaped prion proteins, and agitating the solution to encourage any abnormal prion “seeds” in the tissue to latch onto the regular proteins. If even trace amounts of pathogenic protein are present, they rapidly use the normal proteins to create millions of insoluble, fibrous amyloid strands. Researchers believe that these amyloid aggregates, also seen in other neurodegenerative diseases such as Alzheimer’s disease, ultimately cause CJD by interfering with or killing off neurons en masse. After death, the brains of people affected by CJD are so badly damaged that they often resemble Swiss cheese or sponges.

The RT-QuIC test, now being used in diagnostic centers around the world, works well but still misses about 10% to 20% of cases, Caughey says. It also requires an invasive, potentially painful spinal tap. In the new study, the researchers ran a fiber optic scope straight up patients’ noses to the very top of the nasal cavity where olfactory neurons are located. In theory, these neurons should contain much higher levels of abnormal prion protein tangles than does CSF because they are directly connected to the brain, Caughey notes. Then, the scientists rolled a small brush along the roof of the nasal vault and analyzed the samples of discharge or tissue they collected with the RT-QuIC assay.

As predicted, the concentration of abnormal prions detected in the nasal samples was several orders of magnitude higher than those found in CSF, the group reports online today in The New England Journal of Medicine (NEJM). Compared with the CSF-based method, which correctly identified only about 77% of positive cases in this study, the swab test caught 97% of 30 CJD-positive patients, missing just one. In addition, the nasal brushings produced no false negative results in 45 disease-free controls, Caughey says.

“Much higher numbers of patients and controls need to be tested to work out the actual diagnostic sensitivity” of the test, but it appears to be a promising way of detecting CJD without performing an invasive procedure, Caughey says. One of his colleagues underwent the nasal brush test, he says, and although it was not exactly a pleasant experience, “there’s not much pain involved, apparently.”

“This is a big advance,” says Pierluigi Gambetti, a neuropathologist at Case Western Reserve University in Cleveland, Ohio. In principle, the nasal brush test should make it possible to diagnose the disorder much earlier than the CSF–based technique because abnormal prions build up in olfactory neurons more quickly than they migrate out of the brain into spinal fluid, he says.

Gambetti, who was not involved in the new study, is co-author on a second NEJM paper appearing online today that shows that an assay similar to the CSF–based RT-QuIC test can pick up very small amounts of abnormal prion protein in the urine of people who have contracted a rare variant of CJD that is transmitted by consuming contaminated meat. A handful of such cases have recently been diagnosed in the United States, he notes, and the urine test could be another quick, affordable way to screen for the disease.

Although these new diagnostic methods may help prevent CJD from spreading, they can do little for patients themselves, Caughey says. “Hopefully someday we’ll have a therapy” so that clinicians can intervene before too much damage is done.