MAPT and Cognitive impairment: While the precise temporal relationship between these core pathologies remains a topic of debate, it is indisputable that tau tangles are strongly associated with neuronal loss and cognitive impairments in both the preclinical and clinical stages of AD (Arriagada et al., 1992; Hardy and Higgins, 1992; Jack et al., 2013; Ossenkoppele et al., 2016; Bierbrauer et al., 2020).