Post-transcriptional regulation plays a central role in the development and maintenance of the nervous system. Defects in post-transcriptional regulation lead to neurodegenerative diseases. Mounting evidence suggests that the impaired post-transcriptional regulation of associated genes contribute to the neurodegenerative process, such as Alzheimer's disease (AD). This review discusses the role of disruption of alternative splicing regulation of the human tau gene (MAPT) and alterations of microRNA expression in the pathogenesis of neurodegeneration including AD. A brief overview is provided for the role and the mechanism of post-transcriptional regulation in AD pathogenesis.