CSF Tau Protein in Alzheimer’s Disease and other Neurological and Psychiatric Diseases

Total tau (T-tau) in the Cerebrospinal Fluid (CSF) is among the most reliable markers for the diagnosis of Alzheimer’s disease (AD). However, the high inter-center variation in biomarker concentrations points to the need for setting up specific diagnostic cut-offs for each population. We analyzed the level of T-tau in the CSF of 490 patients affected by AD or other neurological and psychiatric diseases, among the Israeli population. The T-tau levels were significantly higher in the AD group than in the other non-AD diseases, particularly in the other common dementia Fronto Temporal Dementia (FTD), as well as in psychiatric diseases. Receiver-Operating-Characteristic (ROC) analysis provided a ?240 pg/ml cut-off for discrimination between AD and other non-AD diseases {sensitivity 68%, specificity 60%, negative-PV (predictive-value) 84.4%}, and psychiatric diseases (60%, 80%, positive-PV 93.4%), and from FTD (60%, 61.1%, positive-PV 85.8%), respectively. In spite of low PVs, T-tau levels in the AD patients were also higher than in vascular-dementia, Parkinson’s-disease, epilepsy, with similar trends relative to multiple-system-atrophy, dementia with Lewy-body-disease, autoimmune and other degenerative diseases, while comparable with metabolic and acute neurological diseases. Our previously reported ?1,000 pg/ml cut-off for Creutzfeldt?Jakob Disease (CJD) diagnosis allows discrimination from AD (sensitivity 75%, specificity 92.7%, PPV 86.56% NPV 85.8%). An inverse correlation was noticed between CSF T-tau levels and Mini-Mental-State-Examination (MMSE) scores in AD and in VD. Using ?240 pg/ml as a cut-off we showed here that the T-tau level in CSF could be an indicator for differentiation of AD from psychiatric diseases and from FTD in our population. While also informative at ?1000 pg/ml for CJD, the T-tau level was less informative for discrimination of AD from other neurological diseases. Combining the T-tau level in the CSF with other parameters (additional CSF markers, as well as genetic and clinical, including imaging parameters) may provide a stronger indication for AD.