It is intended to provide an inhibitor for the formation of a .gamma.-secretase complex which comprises a cholesterol synthesis inhibitor or a protein geranylgeranylation regulator as the active ingredient; and use of a cholesterol synthesis inhibitor or a protein geranylgeranylation regulator for producing the same. It is also intended to provide a method of screening a substance having an effect of inhibiting the formation of an active complex of .gamma.-secretase which comprises assaying the activity of inhibiting cholesterol synthesis or quantifying cholesterol accumulated in lipid rafts in cells. It is also intended to provide a method of screening a cholesterol synthesis inhibitor, a protein geranylgeranylation regulator or an HMG-CoA reductase inhibitor which comprises assaying the effect of inhibiting the formation of an active complex of .gamma.-secretase. Moreover, it is intended to provide a method of screening an effect of a test substance on .gamma.-secretase which comprises measuring the distribution of constituents (niscastrin, APH-1, Pen-2 and so on) required by .gamma.-secretase for the formation of its active complex in cells.