In humans, loss-of-function mutations in presenilin-1/2 (PS1/PS2), ubiquilin-2/4 (UBQLN2/UBQLN4), or leucine-rich repeat kinase 2 are primary causes of familial AD, ALS, and PD, respectively (118, 216–220). This evidence concerns the gene PSEN1 and amyotrophic lateral sclerosis.