MAPT and Cognitive impairment: This appears to be an important event in human AD brains, as activated calpain-2 is seen in association with neurofibrillary tangles (Adamec et al., 2002; Grynspan et al., 1997; Nixon, 2003), and upregulation of calpain activity heralds tau pathology (Kurbatskaya et al., 2016) and correlates with cognitive deficits (Ahmad et al., 2018).