{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["16(8)"],"submitter":["Lai R"],"pubmed_abstract":["<b>Rationale:</b> Clinical trials for Alzheimer's disease (AD) often yield inconsistent results despite promising preclinical findings. Inhibition of 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), a cortisone reductase, has demonstrated neuroprotective effects in preclinical models. However, clinical outcomes have varied. A potential explanation is the limited representation of <i>apolipoprotein E ε4</i> (<i>APOE4</i>) carriers in preclinical studies, despite evidence that <i>APOE4</i> alters stress responses and glucocorticoid regulation. We hypothesized that <i>APOE4</i> status modulates the efficacy of HSD11B1 inhibition by influencing cortisol metabolism and AD pathology. <b>Methods:</b> We conducted a genetic association study to test whether <i>HSD11B1</i> variants are linked to "],"journal":["Theranostics"],"pagination":["4113-4127"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12905795"],"repository":["biostudies-literature"],"pubmed_title":["Why 11β-HSD1 inhibitors show variable efficacy in Alzheimer's therapy: an APOE4-dependent HSD11B1 mechanism."],"pmcid":["PMC12905795"],"pubmed_authors":["Chung R","Juang J","Lai R","Shie F","Hsu PW","Chen Y","Lam K"],"additional_accession":[]},"is_claimable":false,"name":"Why 11β-HSD1 inhibitors show variable efficacy in Alzheimer's therapy: an APOE4-dependent HSD11B1 mechanism.","description":"<b>Rationale:</b> Clinical trials for Alzheimer's disease (AD) often yield inconsistent results despite promising preclinical findings. Inhibition of 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), a cortisone reductase, has demonstrated neuroprotective effects in preclinical models. However, clinical outcomes have varied. A potential explanation is the limited representation of <i>apolipoprotein E ε4</i> (<i>APOE4</i>) carriers in preclinical studies, despite evidence that <i>APOE4</i> alters stress responses and glucocorticoid regulation. We hypothesized that <i>APOE4</i> status modulates the efficacy of HSD11B1 inhibition by influencing cortisol metabolism and AD pathology. <b>Methods:</b> We conducted a genetic association study to test whether <i>HSD11B1</i> variants are linked to ","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026","modification":"2026-07-16T00:08:43.925Z","creation":"2026-07-09T10:26:00.373Z"},"accession":"S-EPMC12905795","cross_references":{"pubmed":["41695490"],"doi":["10.7150/thno.126244"]}}