TAU Thr231 phosphorylation as a potential Alzheimer's disease biomarker

• Autor(a) principal: Santos, Joana Rita Faneca
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/22056
• topic: Doença de Alzheimer; Fosforilação; Marcadores bioquímicos; Diferenciação celular

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of extracellular amyloid plaques (senile plaques) and intracellular neurofibrillary tangles formed by hyperphosphorylated TAU protein. TAU protein when hyperphosphorylated loses the ability to bind to microtubules and can be released into peripheral fluids. This process leads to neuronal degradation and neuronal death. Phosphorylation at threonine 231 has been shown to be specific for AD and to precede assembly of paired helical filaments in the human brain. In order to understand more about this residue we analysed SH-SY5Y cells undifferentiated and in differentiated cells induced by retinoic acid (RA). Treatment with RA increased expression of TAU phosphorylated at Thr231 (TAUpThr231) as determined by Western blot analysis. We further explored TAU phosphorylation by immunocytochemistry and noticed that in undifferentiated SH-SY5Y cells, TAUpThr231 was located mainly in the nucleus. In contrast, TAU and TAUpThr231 was redistributed to the neurites and in the soma of SH-SY5Y cells, which were induced to differentiate by retinoic acid (RA). In order to evaluate the potential of TAUpThr231 as a biomarker, we measured TAUpThr231 in CSF by a sandwich enzyme immunoassay and observed that the ratio of TAUpThr231/TAU levels discriminated significantly the AD group for the non-AD group. These findings indicate that TAUpThr231/t-TAU ratio levels may be a valuable marker for the clinical diagnosis of AD, irrespective of age and gender.