Isidre Ferrer

By José Luis Albasanz, Carlos Alberto Castillo, Marta Barrachina, Isidre Ferrer and Mairena Martín

Part of the book: The Clinical Spectrum of Alzheimer's Disease

By Marta Barrachina, Mairena Martín, Francisco Ciruela and Isidre Ferrer

Part of the book: Towards New Therapies for Parkinson's Disease

By Alba Naudí, Mariona Jové, Victòria Ayala, Omar Ramírez, Rosanna Cabré, Joan Prat, Manuel Portero-Otin, Isidre Ferrer and Reinald Pamplona

Part of the book: Lipid Peroxidation

By Ester Aso and Isidre Ferrer

Part of the book: Understanding Alzheimer's Disease

By J. Luna-Muñoz, A. Martínez-Maldonado, V. Ibarra-Bracamontes, M. A. Ontiveros-Torres, I. Ferrer, B. Floran-Garduño, M. del C. Cárdenas- Aguayo, R. Mena and M.A. Meraz Ríos

Part of the book: Neurochemistry

By Franc Llorens, Anna Villar-Piqué, Niccolò Candelise, Isidre Ferrer and Inga Zerr

Tau is a microtubule-associated protein, whose main function is the modulation of the stability of axonal microtubules. In physiological conditions tau is abundant in neurons while its expression in glial populations is low and restricted to astrocytes and oligodendrocytes. The aggregation of tau in neurofibrillary or gliofibrillary tangles is the main hallmark of tauopathies, a complex group of human neurodegenerative conditions where tau hyper-phosphorylation causes its increased insolubility and aggregation leading to tangle formation and microtubule destabilization. Tau can be detected in biological fluids in physiological and pathological conditions. In several neurodegenerative dementias, either associated or not to a primary tauopathy, tau levels are altered in a disease-specific pattern, which can be used as a biomarker for disease diagnosis and prognosis. The study of tau levels in biological fluids has been mainly performed in the cerebrospinal fluid (CSF), although the recent development of ultrasensitive techniques allows the robust quantification of tau in blood-based biofluids such as serum and plasma. The presence of elevated total-tau in the CSF is assumed to reflect the degree of axonal damage in the brain tissue. Consequently, highest total-tau CSF levels are found in sporadic Creutzfeldt-Jakob disease, which is characterized by massive neuronal damage and a rapid progressive course. Elevated total-tau is also detected in Alzheimer’s disease and dementia with Lewy bodies, while in other dementia conditions such as vascular dementia, frontotemporal dementia and corticobasal degeneration are unchanged, inconclusive or not determined. Additionally, total-tau rises temporarily due to cerebral infarction. In contrast, elevated phospho-tau levels seem to be restricted to Alzheimer’s disease pathology, most likely mirroring the presence of the hyper-phosphorylated form in the brain tissue, although phospho-tau levels are mainly unaffected in tauopathies. Additionally, isoforms and different structural and truncated tau forms have also been reported to be altered in neurodegenerative dementias. In this complex scenario the diagnostic accuracy of diverse tau forms as disease-specific biomarkers needs to be established. In this chapter, we summarize the current knowledge on the alterations of diverse tau forms in biological fluids of neurodegenerative dementias and its relevance in the differential diagnostic context. Additionally, we explore how tau alterations in the brain tissue may explain the etiology of its regulated levels in CSF and blood.

Part of the book: Cognitive Disorders