Alzheimer’s disease is a neurodegenerative process whose origin is unknown. It has been associated with this process at least two important proteins: the first is the β-amyloid forming amyloid plaques and the second protein is Tau, which has been determined to precipitates inside the neuron because hyperphosphorylation, causing instability in the axon. Tau microtubule-associated protein (MAP) is essential for the development of neuronal cell polarity. Tau protein is preferentially localized in the axons, whereas MAP2, another neuronal specific microtubule-associated protein, is localized in the somatodendritic domain. Previous studies have demonstrated that the localization of these proteins depends, at least in part, on messenger RNA (mRNA) subcellular localization, that is, Tau mRNA into the axon and MAP2 mRNA into the dendrite. Tau protein has an essential role in the pathology of Alzheimer’s disease, and hyperphosphorylated Tau promotes destabilization of microtubules. Tau alternative splicing generates six isoforms in the adult human brain due to the inclusion or exclusion of exons 2, 3, and 10. The failure in the splicing process of exon 10 generates a tauopathy, which can be carried out by the amyloid peptide; however, the splicing of other exons is less studied. The impact of amyloid peptide on the alternative splicing of exons 2, 3, and 6 caused formed cell processes to retract in differentiated cells and altered the expression of exons 2/3 in cell culture. Expression of exon 6 was repressed under β-amyloid treatment. The molecular mechanism for this amyloid-Tau interaction remains to be determined, but may have potential implications for the understanding of the underlying neuropathological processes in Alzheimer’s disease.
Part of the book: Update on Dementia