APOE and Alzheimer disease: Within the spectrum of Alzheimer’s disease phenotypes, the rapidly progressive subtype is characterized by rapid cognitive decline [4,7,11], a higher frequency of missense variants in known AD risk genes [1], a low frequency of the e4 allele of the APOE gene [4], and an accumulation of amyloid beta and misfolded tau proteins with distinct conformational characteristics [3,27,50] and interactomes [7,13,14].