PSEN1 and Alzheimer disease: Indeed, Aβ42 peptide immunization studies in AD patients have revealed that Aβ43-positive plaques can be cleared without a concomitant increase in vascular Aβ43 deposition [28], and the increased Aβ43 levels generated by mutant presenilin-1 alleles can be counteracted using small molecule γ-secretase modulators [89].