**6. Conclusion**

CSF t-tau and p-tau concentrations display good sensitivity and specificity in the discrimination of AD patients from non-demented control cases and a high diagnostic accuracy in the discrimination of sCJD cases. Both biomarkers become useful in the identification of patients at risk of progression to AD. The partial overlap between t-tau and p-tau levels among several neurodegenerative dementias indicates that more specific biomarkers are required in order to improve the accuracy in the differential diagnostic context. Alternative tau-based approaches have been recently developed and form the basis of the second-generation tau assays. On one side, the use of composite biomarkers, the development of non-p-tau assays and tau seeding methodologies, and the detection of tau truncated forms and alternative phosphorylation sites are promising alternatives that need further research to maximize their potential as diagnostic and prognostic tools. On the other side, the quantification of tau in blood-based fluids is gaining experimental momentum due to the advantages of using blood instead of CSF and to the implementation of high-sensitivity tests that can detect scarce tau amounts in plasma and serum. Several contradictory findings in the field might be related to the use of differential methodologies, which in some of the cases are not yet fully implemented and validated in large and independent cohorts.

might provide important clues toward understanding the molecular events taking place in

**Table 1.** Tau levels in the biological fluids of major neurodegenerative diseases and associated disorders compared to

Tau Protein as a Biological Fluid Biomarker in Neurodegenerative Dementias

http://dx.doi.org/10.5772/intechopen.73528

79

A summary of the findings on tau-related biomarkers in the CSF and blood of neurodegenera-

This study was funded by the Spanish Ministry of Health - Instituto Carlos III (Miguel Servet - CP16/00041) to FL, by the Red Nacional de priones (AGL2015-71764-REDT- MINECO) to FL, IZ and IF, by the Robert Koch Institute through funds from the Federal Ministry of Health (grant no. 1369–341) to IZ, by the Spanish Ministry of Health, Instituto Carlos III (Fondo de Investigación Sanitaria - FIS PI11/00968, FIS PI14/00757) to IF. AV-P is funded by a Dorothea

neurodegenerative processes.

control cases.

**Acknowledgements**

tive dementias is shown in **Table 1**.

Schlözer Scholarship (Georg August University – Göttingen).

Finally, the clinical diagnostic utility of tau measurements is complemented by the role of this protein as a reporter of the degree of neuro-axonal damage in the brain and the pathological hyper-phosphorylation tau state, which is specifically present in tauopathies. Since we are in the dawning of second-generation tau assays, future studies are necessary to validate them in larger and independent cohorts of patients in order to prove their clinical utility while they


**Table 1.** Tau levels in the biological fluids of major neurodegenerative diseases and associated disorders compared to control cases.

might provide important clues toward understanding the molecular events taking place in neurodegenerative processes.

A summary of the findings on tau-related biomarkers in the CSF and blood of neurodegenerative dementias is shown in **Table 1**.
