But in AD and related neurodegenerative diseases, significantly increased HDAC6 reduces tubulin acetylation, as a result, tau is hyperphosphorylated and aggregates into neurofibrillary tangles, which eventually leads to neuron loss, synaptic dysfunction, and cognitive decline (Hempen and Brion, 1996; Yan, 2014; Tiwari et al., 2019; Li et al., 2021). This evidence concerns the gene MAPT and Alzheimer disease.