{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:03:15Z","timestamp":1790996595069,"version":"4.1.0"},"reference-count":364,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T00:00:00Z","timestamp":1685836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010473","name":"Alzheimer\u2019s Foundation of America Award","doi-asserted-by":"publisher","award":["AWD00004772"],"award-info":[{"award-number":["AWD00004772"]}],"id":[{"id":"10.13039\/100010473","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010473","name":"Alzheimer\u2019s Foundation of America Award","doi-asserted-by":"publisher","award":["AG066512"],"award-info":[{"award-number":["AG066512"]}],"id":[{"id":"10.13039\/100010473","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010473","name":"Alzheimer\u2019s Foundation of America Award","doi-asserted-by":"publisher","award":["AG060882"],"award-info":[{"award-number":["AG060882"]}],"id":[{"id":"10.13039\/100010473","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH grants","award":["AWD00004772"],"award-info":[{"award-number":["AWD00004772"]}]},{"name":"NIH grants","award":["AG066512"],"award-info":[{"award-number":["AG066512"]}]},{"name":"NIH grants","award":["AG060882"],"award-info":[{"award-number":["AG060882"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>As the search for modalities to cure Alzheimer\u2019s disease (AD) has made slow progress, research has now turned to innovative pathways involving neural and peripheral inflammation and neuro-regeneration. Widely used AD treatments provide only symptomatic relief without changing the disease course. The recently FDA-approved anti-amyloid drugs, aducanumab and lecanemab, have demonstrated unclear real-world efficacy with a substantial side effect profile. Interest is growing in targeting the early stages of AD before irreversible pathologic changes so that cognitive function and neuronal viability can be preserved. Neuroinflammation is a fundamental feature of AD that involves complex relationships among cerebral immune cells and pro-inflammatory cytokines, which could be altered pharmacologically by AD therapy. Here, we provide an overview of the manipulations attempted in pre-clinical experiments. These include inhibition of microglial receptors, attenuation of inflammation and enhancement of toxin-clearing autophagy. In addition, modulation of the microbiome-brain-gut axis, dietary changes, and increased mental and physical exercise are under evaluation as ways to optimize brain health. As the scientific and medical communities work together, new solutions may be on the horizon to slow or halt AD progression.<\/jats:p>","DOI":"10.3390\/medicina59061084","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T01:53:25Z","timestamp":1685930005000},"page":"1084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Alzheimer\u2019s Disease Treatment: The Search for a Breakthrough"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4478-2441","authenticated-orcid":false,"given":"Allison B.","family":"Reiss","sequence":"first","affiliation":[{"name":"Department of Medicine and Biomedical Research Institute, NYU Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"Muhieddine","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biomedical Research Institute, NYU Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berlin","family":"Jacob","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biomedical Research Institute, NYU Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mesbah","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biomedical Research Institute, NYU Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1148-902X","authenticated-orcid":false,"given":"Aaron","family":"Pinkhasov","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biomedical Research Institute, NYU Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irving H.","family":"Gomolin","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biomedical Research Institute, NYU Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9632-168X","authenticated-orcid":false,"given":"Mark M.","family":"Stecker","sequence":"additional","affiliation":[{"name":"Fresno Institute of Neuroscience, Fresno, CA 93730, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wisniewski","sequence":"additional","affiliation":[{"name":"Center for Cognitive Neurology, Departments of Neurology, Pathology and Psychiatry, NYU School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"De Leon","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biomedical Research Institute, NYU Long Island School of Medicine, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15056","DOI":"10.1038\/nrdp.2015.56","article-title":"Alzheimer\u2019s disease","volume":"1","author":"Masters","year":"2015","journal-title":"Nat. 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