{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:08:35Z","timestamp":1792789715937,"version":"4.5.0"},"reference-count":108,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) has a critical unmet medical need. The consensus around the amyloid cascade hypothesis has been guiding pre-clinical and clinical research to focus mainly on targeting beta-amyloid for treating AD. Nevertheless, the vast majority of the clinical trials have repeatedly failed, prompting the urgent need to refocus on other targets and shifting the paradigm of AD drug development towards precision medicine. One such emerging target is apolipoprotein E (APOE), identified nearly 30 years ago as one of the strongest and most reproduceable genetic risk factor for late-onset Alzheimer\u2019s disease (LOAD). An exploration of APOE as a new therapeutic culprit has produced some very encouraging results, proving that the protein holds promise in the context of LOAD therapies. Here, we review the strategies to target APOE based on state-of-the-art technologies such as antisense oligonucleotides, monoclonal antibodies, and gene\/base editing. We discuss the potential of these initiatives in advancing the development of novel precision medicine therapies to LOAD.<\/jats:p>","DOI":"10.3390\/ijms22031244","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T12:20:26Z","timestamp":1611750026000},"page":"1244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["APOE: The New Frontier in the Development of a Therapeutic Target towards Precision Medicine in Late-Onset Alzheimer\u2019s"],"prefix":"10.3390","volume":"22","author":[{"given":"Anna","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Kantor","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA"},{"name":"Viral Vector Core, Duke University Medical Center, Durham, NC 27710, USA"},{"name":"Duke Center for Advanced Genomic Technologies, Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2529-8785","authenticated-orcid":false,"given":"Ornit","family":"Chiba-Falek","sequence":"additional","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA"},{"name":"Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"ref_1","unstructured":"(2020). 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