Disorders of the Nervous System
Author: Indiana de María Páez Paz | Email: indiana.m.p.p@gmail.com
Indiana de M Páez Paz 1°, Carolina Facal 1°, Monica Mezmezian 4°, Gustavo Sevlever 4°, Tomás Falzone 2°, Blas Couto 3°, Gabriel Mizraji 3°, Avale Elena 1°
1° INGEBI-CONICET
2° IBioBA-CONICET and FMED-UBA
3° INCyT- INECO-CONICET and Hospital Universitario Favaloro
4° Laboratorio de Neuropatología y Biología Molecular, Banco de Cerebros, Fleni
Tauopathies, as Alzheimers disease, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are neurodegenerative diseases characterized by the abnormal metabolism of Tau, which accumulates as insoluble hyperphosphorylated neuronal deposits. In each type of tauopathy, this process starts in certain brain nuclei and repeats a defined progression pattern, which gives rise to different clinical signs and symptoms, but some tauopathies present mixed phenotypes which makes the clinical diagnosis process complicated. Current diagnosis criteria do not absolutely differentiate among tauopathies from each other and from other neurodegenerative diseases. Thus, post-mortem analysis and its correlation with previously observed clinical signs is an utmost need to understand the molecular bases of each type of tauopathy and refine diagnosis.
In this project we address this issue through the analysis of post-mortem brain samples from patients diagnosed with primary tauopathies (PSP/CBD) in Argentina. We analyze the presence of pathological Tau and changes in Tau isoforms contents in different regions of the brain. In further studies, we will determine MAPT mutations and local variants of candidate genes putatively affecting tau processing and their transcriptomic profile. We show here that one patient initially diagnosed with PSP presents an increase in Tau3R isoforms in basal ganglia and prefrontal cortex, suggesting a 3R tauopathy.