Additionally, Fleitas et al. reported upregulation of proBDNF and sortilin in the hippocampus and a higher ratio of proBDNF to mBDNF in the cerebrospinal fluid of patients with AD through a gain-of-function mutation in the PSEN1 gene that may enhance proBDNF-induced cell death [147]. This evidence concerns the gene BDNF and Alzheimer disease.