APP and Cognitive impairment: Despite all the evidence suggesting a causal role of Aβ in AD, including mutations in APP and presenilin 1 and 2 that cause autosomal dominant, early-onset familial AD (FAD) and promote cerebral Aβ accumulation [4], inhibitors of BACE1 or γ-secretase have yielded negative results in clinical trials involving sporadic AD patients with cognitive impairments [33, 34].