In Alzheimer’s disease models, SPRC reduced astrogliosis, lipofuscin accumulation, and the amyloid beta 1–42/amyloid beta 1–40 (Aβ1–42/Aβ1–40) ratio through H2S-associated inhibition of NF-κB and mitogen-activated protein kinase (MAPK) signaling, while increasing CBS activity and H2S concentration. The gene discussed is SPRR3; the disease is early-onset autosomal dominant Alzheimer disease.