HCRT and early-onset autosomal dominant Alzheimer disease: While it is clear that patients with Parkinson’s and Alzheimer’s disease display significant loss of orexin neurons in post-mortem exams, analysis of CSF levels in living patients do not always bear this pattern, suggesting there may be a progressive and possibly sudden loss of central orexin synthesis or compensatory peripheral production (Ripley et al., 2001; Drouot et al., 2003; Baumann et al., 2005; Fronczek et al., 2007, 2012).