MAPT and Alzheimer disease: In the approach towards disease-modifying therapies for common (AD) and very rare causes of PCA (prion disease, GRN, MAPT mutations), salient knowledge gaps include appropriate trial design accommodating extreme phenotypic heterogeneity and the possibility of differing treatment response (e.g. given evidence that PCA patients are less likely to carry APOE ε4 [2, 58]).