Tau alternative splicing in alzheimer’s disease

Abstract

The microtubule-associated protein (MAP) tau is essential for the development of neuronal cell polarity. Tau protein is preferentially localized in the axon, whereas MAP2, another neuron-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 mRNA subcellular localization - of tau mRNA into the axon and MAP2 mRNA into the dendrite. Tau protein plays a pivotal role in the pathophysiology of Alzheimer’s disease, in which its hyperphosphorylation promotes aggregation and microtubule destabilization. Tau undergoes alternative splicing, which generates six isoforms in the human brain, due to the inclusion/exclusion of exons 2, 3 and 10. Dysregulation of the splicing process of tau exon 10 is sufficient to cause tauopathy, and has been shown to be influenced by b -amyloid peptides, while there has been less research conducted on the splicing of other exons. This study found that the effects of β-amyloid (42) on the alternative splicing of tau exon 2/3 and 6 caused formed cell processes to retract in differentiated cells and altered the expression of exon 2/3 in cell culture. Expression of exon 6 was repressed under β-amyloid treatment. Although the molecular mechanism for this amyloid-tau interaction remains to be determined, it may have potential implications for the understanding of the underlying neuropathological processes in Alzheimer’s disease.