Aftin-4 is an inducer of amyloid-β (1-42) (Aβ42). It selectively increases extracellular Aβ42 over Aβ40 production in N2a-AβPP695 cells when used at concentrations ranging from 1 to 100 mM. In vivo, aftin-4 (3-20 nmol/animal, i.c.v.) increases hippocampal Aβ42 content, lipid peroxidation, and production of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in mice. It also induces spatial working and spatial reference memory deficits in mice, effects that are reversed by co-administration of the γ-secretase inhibitor BMS-299,897.
