An analysis of postmortem tissue shows that GDE2 forms aberrant intracellular accumulations in the brain of patients with AD and ALS, and consistent with GDE2 dysfunction in disease, the amounts of membrane-tethered and soluble RECK are respectively increased and decreased in AD brain, and the amounts of GPI-anchored proteins are disproportionately reduced in the cerebrospinal fluid of patients with ALS [23,31]. This evidence concerns the gene GPI and amyotrophic lateral sclerosis.