Résumé
Background
The definite diagnosis of Creutzfeldt‐Jakob disease (CJD) requires a neuropathological examination revealing the presence of the pathogenic prion protein. As a reliable in vivo diagnosis is required for clinical care, without pathological confirmation, diagnostic criteria for CJD have been proposed including neuroimaging, electrophysiology and 14.3.3 protein positivity in cerebrospinal fluid (CSF) but their accuracy remains suboptimal. Tau protein in cerebrospinal fluid was found to be extremely elevated in CJD and the phosphorylated‐Tau to Tau ratio (P‐Tau/Tau) was reported to be decreased for some CJD patients.
Method
We first aimed to evaluate the efficiency of the P‐Tau/Tau ratio to distinguish CJD from other neurodegenerative disorders in a cohort of patients with a rapidly progressive cognitive disorder and high CSF Tau level above 1000 pg/ml. Then, retrospectively gathering 49 CJD patients from 7 French University Hospital, the Alzheimer CSF biomarkers and the P‐Tau/Tau ratio sensitivity were compared to current CJD diagnosis criteria. A P‐Tau/Tau ratio value below 0.075 was considered as indicative of CJD.
Result
The diagnoses in the first cohort of 24 patients were: CJD (n = 11), Alzheimer disease (n = 11), Frontotemporal dementia (n = 1) and a Gayet‐Wernicke’s encephalopathy (GWE) (n = 1). Using the threshold of 0.075, the ratio P‐Tau/Tau correctly categorized all CJD patients and only one patient, with GWE, was wrongly classified (fig. 1). The area under the curve of the P‐Tau/Tau ratio was 95% (IC 95% 0.85‐1.0). In the 49 CJD series, the ratio was abnormal in 100% of the patients, while the clinical criteria were met in 81.6% and 91.7% for neuroimaging, 50% for helectroencephalogram and 55.1% for protein 14‐3‐3.
Conclusion
Alzheimer CSF biomarkers with Tau level and P‐Tau/Tau ratio may increase diagnosis accuracy for positive and differential diagnosis of CJD with a complementary value to current validated diagnosis criteria. They could be particularly helpful in clinical practice for patients with rapid cognitive decline and Tau > 1000 pg/ml or in atypical cases with unmet diagnosis criteria.