Disclosed herein are methods of diagnosing, preventing and treating Alzheimers disease based on the use of an inhibitor for the binding of amyloid-β (Aβ) to FcγRIIb, and a method of screening the inhibitor. The inhibitor is selected from the group consisting of an FcγRIIb protein or a variant thereof, an FcγRIIb extracellular domain, an anti-FcγRIIb antibody, an FcγRIIb-specific peptide and an FcγRIIb-specific siRNA. The inhibitor reduces the toxic signaling and intracellular translocation of Aβ and the neurotoxicity, neuronal cell death and memory impairment mediated by Aβ by inhibiting the binding between Aβ and FcγRIIb. Thus, the inhibitor is useful in the diagnosis, prevention and treatment of Alzheimers disease.
