PSEN1 and Alzheimer disease: This is supported by an observation of increased hippocampal activation measured by functional magnetic resonance imaging (fMRI) during memory-encoding tasks in individuals who carry presenilin-1 (PS1) with E280A mutation or the APOE4 allele, which are well-known genetic risk factors for AD, before the onset of clinical symptoms (Bakker et al, 2012; Bookheimer et al, 2000; Celone et al, 2006; Dickerson et al, 2005; Quiroz et al, 2010; Trivedi et al, 2008).