Aftin-4, an amyloid forty-two inducer, activates γ-secretase, promoting the generation of amyloid-β-1-42 (Aβ1-42) from amyloid-β protein precursor. Aftin-4(Aftin4) increased Aβ-1-42, but not Aβ-1-40 in mouse hipppocampus, accompanied by learning deficits and mitochondrial ultrastructural changes similar to those found in the brains of patients with AD. Aftin-4(Aftin4) can thus be used to induce a rapid, acute Alzheimer's disease-like toxicity in the rodent brain.

Brains of 4-mo-old C57BL/6 wild-type mice were dissected and mechanically disassociated in HBSS with a tissue homogenizer. Aliquots from each mouse were incubated with DMSO and two concentrations of Aftin-4 at 37°C for 3 h. Liquefied brains were sonicated and centrifuged at 13,000 rpm for 15 min. WB analysis was performed using CT695 antibody for soluble Aβ-CTF. They are for reference only.