Both loss and gain of function manipulations to these activity-regulated genes, including Arc, Bdnf, Reln, Egr1 and Ppp3ca, have been associated with cognitive deficits during physiological aging and pathological conditions like dementia, neurodegenerative diseases and neuropsychiatric problems (Nonaka et al., 2014). This evidence concerns the gene RELN and neurodegenerative disease.