A follow-up study by this same group revealed male mice generated from this same above cross (ArKO combined with APP23) have reduced brain plague formation, show improved cognitive functions, increased NEP activity (neprilysin, which mediates Aβ clearance), and reduced expression of BACE1, suggesting in males an increase in endogenous T due to removal of the CYP19 enzyme protects against AD (195). This evidence concerns the gene MME and Alzheimer disease.