Those three sphingolipid hydrolysis enzymes, except for aCDase, are not attenuated at the enzymatic activity level [6,19,20] or at the protein level [21,22] in the non-lesional epidermis or the non-lesional SC from AD skin, although one study did report a decreased activity of aSMase [23]. This evidence concerns the gene SMPD1 and Alzheimer disease.