Importantly, using GGA3+/− mice we have demonstrated that a 50% reduction in GGA3 (as has been identified in the brains of AD patients) is sufficient to cause a sustained elevation of BACE1 levels and activity and Aβ production in sub-acute phase (7days) of injury when GGA1 levels have returned to normal. The gene discussed is BACE1; the disease is Alzheimer disease.