A noninvasive test for human prion disease using hair roots and scalp

Invasive tests like cerebrospinal fluid (CSF) examination are highly effective for diagnosing human prion disease (HPD). Real-time quaking-induced conversion (RT-QuIC) CSF assay demonstrates 80–90% sensitivity for HPD diagnosis. To establish a minimally invasive diagnostic approach, we evaluated RT-QuIC testing on hair root and scalp samples. We collected scalp samples from 22 HPD and 5 non-HPD patients during pathological examinations and analyzed them using RT-QuIC assay and neuropathological methods. In our prospective study, hair root and CSF samples from 300 patients were tested using RT-QuIC assay along with other biomarkers, including 14-3-3 protein, total tau protein, RT-QuIC CSF assay, and MRI findings. All 22 HPD patients demonstrated positive prion seeding activity in scalp and hair root RT-QuIC assays. Neuropathological examination in one HPD patient revealed abnormal prion protein in scalp tissue. Among 177 HPD patients diagnosed by Japan Prion Surveillance Committee and 123 non-HPD patients, RT-QuIC assay of hair roots demonstrated sensitivity and specificity of 45.8% and 100%, respectively. Sensitivities of 14-3-3 protein, total tau protein, RT-QuIC CSF assay, and MRI findings were 83.1%, 86.4%, 74.6%, and 100%, respectively, with specificities of 65.0%, 65.0%, 100%, and 56.1%, respectively. RT-QuIC assays could be developed into novel diagnostic methods for neurodegenerative diseases.