Initial evidence for an involvement of HTRA1 in amyloid aggregation diseases was presented in biochemical in vitro studies showing HTRA1-dependent degradation of Aβ and tau, the principal components of AD-associated amyloid plaques and neurofibrillary tangles (Grau et al., 2005; Tennstaedt et al., 2012; Poepsel et al., 2015). Here, HTRA1 is linked to Alzheimer disease.