{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:14:27Z","timestamp":1783415667052,"version":"3.54.6"},"reference-count":39,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Ministry of Health & Welfare, Republic of Korea","award":["RS-2025-02223212"],"award-info":[{"award-number":["RS-2025-02223212"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is characterized by a neuropathological cascade that begins with amyloid-\u03b2 (A\u03b2) deposition. The recent success of disease-modifying drugs targeting A\u03b2 has demonstrated that modulating amyloidopathy can yield clinical benefits, underscoring the need for additional drugs affecting amyloid pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify novel drug targets associated with A\u03b2 accumulation in AD using Mendelian randomization (MR) analysis of the druggable genome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed MR analysis on expression quantitative trait loci (eQTLs) of the druggable genome in relation to A\u03b2 accumulation using summary-data-based MR (SMR). Blood eQTL data were obtained from the eQTLGen consortium, and brain eQTL data from BrainMeta and PsychENCODE, while A\u03b2 positron emission tomography (PET) genome-wide association study data were derived from 11,816 non-Hispanic White participants across 13 cohorts. Co-localization analysis was conducted to enhance the reliability of the MR results, and additional validation was performed using blood and brain protein quantitative trait loci (pQTLs) as instrumental variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The SMR and co-localization analyses revealed causal associations between the druggable genome and A\u03b2 accumulation, with\n                      <jats:italic toggle=\"yes\">APH1B<\/jats:italic>\n                      identified in blood eQTL data and\n                      <jats:italic toggle=\"yes\">ACE<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">APH1B<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">CR1<\/jats:italic>\n                      identified in brain eQTL data. Further analysis using pQTL data confirmed causal associations for ACE and CR1, with ACE showing a negative association with A\u03b2 PET uptake.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings highlight potential target genes for AD treatment, and the protective effect of\n                      <jats:italic toggle=\"yes\">ACE<\/jats:italic>\n                      against amyloid pathology suggests that alternative medications to ACE inhibitors may be preferred for blood pressure management in the context of AD. Overall, our study demonstrates the potential of MR to facilitate drug repurposing for AD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261454540","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:20:14Z","timestamp":1780046414000},"page":"1016-1025","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetically prioritized druggable targets for amyloid-\u03b2 pathology highlight\n                    <i>ACE<\/i>\n                    as a therapeutic candidate in Alzheimer's disease"],"prefix":"10.1177","volume":"112","author":[{"given":"Jun Pyo","family":"Kim","sequence":"first","affiliation":[{"name":"Samsung Medical 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