GRN and Alzheimer disease: The link between PGRN and AD are supported by genetics, where several GRN mutations in human studies have been associated with increased risk for AD, including a null mutation IVSO + 5G > C, the GRN nonsense mutation p.Arg535X [7], two missense mutations, p.Cys139Arg and p.Pro451Leu [8] and the exon 1 GRN mutations, p.Gly35Arg and pASP33Asp [9].