Síntesis y evaluación de ligandos tau-selectivos basados en estructuras de oxindol como potenciales agentes de imagen PET para diagnóstico in vivo de la Enfermedad de Alzheimer y otras tauopatías

Resum

Alzheimer ’s disease (AD) belongs to the pathology group named Taupathies. Currently, more than 24 million people suffer from Alzheimer disease and other dementias. This represents a serious health problem, especially if we take into account that the diagnosis of AD can only be confirmed by a postmortem histological analysis. So we need more effective and non-invasive techniques for early diagnosis.AD presents two biomarkers: tau protein and amyloid β peptide. Tau protein is the main microtubule-associated protein, responsible for axonal stabilization, which allows the proper neuronal transport. In its aberrant form, tau undergo a process of hyperphosphorilation that leads to an abnormal aggregation, forming Paired Helicoidal Filaments (PHFs) and Neurofibrillary Tangles (NFTs) in the intraneuronal medium. This process drives to the loss of the biological activity of tau and as a consequence, the cognitive decline. In addition, the other biomarker in Alzheimer's disease, the β-amyloid peptide aggregates as an extracellular deposit, forming senile plaques (SPs), which can trigger a local inflammatory response...