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Despite efforts to effectively treat the disease, only seven drugs are approved for its treatment, and only two of these prevent its progression. This highlights the need to identify new pharmacological options. This review focuses on mimetic peptides, small molecule correctors and HAE\u20104 antibodies that target ApoE. These drugs reduce \u03b2\u2010amyloid\u2010induced neurodegeneration in preclinical models. In addition, loop diuretics such as bumetanide and furosemide show the potential to reduce the prevalence of Alzheimer's disease in humans, and antidepressants such as imipramine improve cognitive function in individuals diagnosed with Alzheimer's disease. Consistent with this, both classes of drugs have been shown to exert neuroprotective effects by inhibiting ApoE4\u2010catalysed A\u03b2 aggregation in preclinical models. Moreover, peroxisome proliferator\u2010activated receptor ligands, particularly pioglitazone and rosiglitazone, reduce ApoE4\u2010induced neurodegeneration in animal models. However, they do not prevent the cognitive decline in APOE \u03b54 allele carriers. Finally, ApoE4 impairs the integrity of the blood\u2013brain barrier and haemostasis. On this basis, ApoE4 modulation is a promising avenue for the treatment of late\u2010onset Alzheimer's disease.<\/jats:p>","DOI":"10.1111\/bcpt.14055","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:43:55Z","timestamp":1721263435000},"page":"237-249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Drugs targeting APOE4 that regulate beta\u2010amyloid aggregation in the brain: Therapeutic potential for Alzheimer's disease"],"prefix":"10.1111","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8392-6026","authenticated-orcid":false,"given":"Joan","family":"Poblano","sequence":"first","affiliation":[{"name":"Faculty of Chemical Sciences Autonomous University of Coahuila  Saltillo Coahuila 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