Most importantly,these alterations appear to be isoform-specific and brain region-specific.As stated by Kelly in a recent review, “not all studies identifyan upregulation of cAMP-PDE expression or activity in AD patient andmodel studies”, but preclinical and clinical evidence supportingthe potential of PDE inhibitors is emerging.11 In similar ways, decreased cGMP signaling can be associated withaging. The gene discussed is ALDH7A1; the disease is Alzheimer disease.