The latter phenomenon, saturation of inhibition, may be related to variable drug bioavailability, drug metabolism, or cellular responsivity. Our present data do not shed any light on the mechanism of saturation in some cell lines. We note that saturation could be related to the same mechanisms underlying variable response to inhibitors. Either way, these data indicate that evaluating dose-responses of candidate anti-amyloid therapeutics may require individualized testing based on cellular responses or yet-to-be determined genetic markers. Identification of single-nucleotide polymorphism (SNP) that correlates with cellular responses may provide important mechanistic and clinical information.
