Diagnosis associated with Tau higher than 1200 pg/mL: Insights from the clinical and laboratory practice

Context: Cerebrospinal fluid (CSF) biomarkers are valuable tools for the diagnosis of neurological diseases. We aimed to investigate within a retrospective multicentric study the final diagnosis associated with very high CSF Tau levels and to identify patterns of biomarkers that would differentiate them in clinical practice, to help clinical biologists into physicians' counseling. Patients and methods: Within the national multicentric network ePLM, we included 1743 patients from January 1, 2008, to December 31, 2013, with CSF biomarkers assayed by the same Innotest assays (protein Tau, phospho-Tau [pTau], and A beta 1-42). We identified 205 patients with protein Tau concentration higher than 1200 pg/mL and final diagnosis. Results: Among those patients, 105 (51.2%) were suffering from Alzheimer's disease, 37 (18%) from sporadic Creurtfeldt-Jakob disease, and 63 (30.7%) from other neurological diseases including paraneoplastic/central nervous system tumor, frontotemporal dementia, other diagnoses, amyloid angiopathy, Lewy body dementia, and infections of the central nervous system. Phospho-Tau, A beta 1-42 and A beta 1-42/pTau values differed significantly between the three groups of patients (p <.001). An A beta 1-42/pTau ratio between 4.7 and 9.7 was suggestive of other neurological diseases (threshold in AD: 8.3). CSF 14-3-3 was useful to discriminate Alzheimer's disease from Creurtfeldt-Jakob disease in case of A beta 1-42 concentrations < 550 pg/mL or pTau > 60 pg/mL. Conclusion: This work emphasizes the interest of a well-thought-out interpretation of CSF biomarkers in neurological diseases, particularly in the case of high Tau protein concentrations in the CSF.