**3.1. Genetic mutations of tau**

#### *3.1.1. Tau mutations in neurodegenerative disorders*

Genetic mutations of tau can cause familial tauopathies, which are commonly found in frontal temporal dementia (FTD), including a range of clinical conditions like Pick's disease, corticobasal dementia, and progressive supranuclear palsy [63, 64]. Mutations of tau were first discovered in the late 1990s in inherited FTD families [65], and it was the first known monogenic mutations that could cause FTD [63, 64]. Epidemiological surveys showed MAPT mutations are responsible for 5–20% FTD cases [63]. Since MAPT is localized to chromosome 17 and the subject showed FTD with parkinsonism syndrome, it was named frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) to refer tau mutations-associated FTD [66]. More than a hundred tau mutations have been identified, and not all of them are pathogenic. A detailed mutations list and their associated impacts can be found online at Alzforum. org [67]. Tau mutations are rarely found in Alzheimer's disease (AD) and normally are not considered as a major genetic risk factor for the disease's familial form. But certain mutations could contribute to the pathogenesis of AD, and some found that mutations' pathogenicity has not been integrated yet [67, 68].
