Finally, all the transgenic mouse models discussed are based on the expression of mutant genes implicated in causing AD in a relatively small subset of patients. Except for their generally early age of onset, these familial cases appear to phenocopy quite well the clinical and pathological features of sporadic cases, but it remains possible that the mutations themselves introduce effects that are not found in the sporadic disease. In particular, presenilins affect a range of biological functions through effects that are not dependent on their role in γ-secretase activity, and at least some of these activities are known to be altered by FAD mutants.23
