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Unlike conventional anti-inflammatory drugs, these compounds have multitargeted effects, including their ability to inhibit amyloid fibril formation. However, few studies have explored their efficacy in high-validity AD models. Female APPswe\/PS1E9 (APP\/PS1) mice and their wild-type (WT) littermates were orally administered with fullerene C60 (0.1 mg\/kg\/day) or fullerenol C60(OH)24 (0.15 mg\/kg\/day) for 10 months starting at 2 months of age. Behavioral assessments were performed at 12 months of age. Amyloid plaque density and size were analyzed in the brain regions using Congo red staining. The expression of genes related to inflammation and plasticity was examined, and an in vitro assay was used to test the toxicity of fullerenol and its effect on amyloid \u03b2 peptide 42 (A\u03b242)-induced reactive oxygen species (ROS) production. Fullerenol reduced the maximum plaque size in the cortex and hippocampus, decreased the small plaque density in the hippocampus and thalamus, and prevented an increase in glial fibrillary acidic protein (GFAP) positive cell density in the mutants. Both treatments improved cognitive and emotional behaviors and reduced Il1\u03b2 and increased Sirt1 expression. In vitro, fullerenol was non-toxic across a range of concentrations and reduced A\u03b242-induced ROS production in brain endothelial cells and astrocytes. Long-term administration of fullerene or fullerenol improved behavioral and molecular markers of AD in APP\/PS1 mice, with fullerenol showing additional benefits in reducing amyloid burden.<\/jats:p>","DOI":"10.3390\/antiox14070834","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T09:12:48Z","timestamp":1751965968000},"page":"834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Distinctive Effects of Fullerene C60 and Fullerenol C60(OH)24 Nanoparticles on Histological, Molecular and Behavioral Hallmarks of Alzheimer\u2019s Disease in APPswe\/PS1E9 Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6161-1671","authenticated-orcid":false,"given":"Sholpan","family":"Askarova","sequence":"first","affiliation":[{"name":"Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kseniia","family":"Sitdikova","sequence":"additional","affiliation":[{"name":"Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"},{"name":"Institute of General Pathology and Pathophysiology, Moscow 125315, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3670-3600","authenticated-orcid":false,"given":"Aliya","family":"Kassenova","sequence":"additional","affiliation":[{"name":"Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"},{"name":"Department of General Biology and Genomics, Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0258-1879","authenticated-orcid":false,"given":"Kirill","family":"Chaprov","sequence":"additional","affiliation":[{"name":"Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka 119071, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-574X","authenticated-orcid":false,"given":"Evgeniy","family":"Svirin","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, Moscow 125315, Russia"},{"name":"Neuroplast BV, 6222 NK Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3818-3079","authenticated-orcid":false,"given":"Andrey","family":"Tsoy","sequence":"additional","affiliation":[{"name":"Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7583-1464","authenticated-orcid":false,"given":"Johannes","family":"de Munter","sequence":"additional","affiliation":[{"name":"Neuroplast BV, 6222 NK Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gorlova","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, Moscow 125315, Russia"},{"name":"Research and Education Resource Center, Peoples Friendship University of Russia, Moscow 117198, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0460-4992","authenticated-orcid":false,"given":"Aleksandr","family":"Litavrin","sequence":"additional","affiliation":[{"name":"Department of Normal Physiology, Sechenov First Moscow State Medical University, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksei","family":"Deikin","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Technology and Gene Editing for Biomedicine and Veterinary, National Research, Belgorod State University, Belgorod 308015, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Nedorubov","sequence":"additional","affiliation":[{"name":"Department of Normal Physiology, Sechenov First Moscow State Medical University, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8765-3386","authenticated-orcid":false,"given":"Nurbol","family":"Appazov","sequence":"additional","affiliation":[{"name":"Laboratory of Engineering Profile Physical and Chemical Methods of Analysis, Korkyt Ata Kyzylorda University, Kyzylorda 120014, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Kalueff","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics, Suzhou Municipal Key Laboratory of Neurobiology and Cell Signaling, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Chernopiatko","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, Moscow 125315, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Strekalova","sequence":"additional","affiliation":[{"name":"Institute of General Pathology and Pathophysiology, Moscow 125315, Russia"},{"name":"Research and Education Resource Center, Peoples Friendship University of Russia, Moscow 117198, Russia"},{"name":"Department of Normal Physiology, Sechenov First Moscow State Medical University, Moscow 119991, Russia"},{"name":"Laboratory of Engineering Profile Physical and Chemical Methods of Analysis, Korkyt Ata Kyzylorda University, Kyzylorda 120014, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13195-016-0188-8","article-title":"Recent global trends in the prevalence and incidence of dementia, and survival with dementia","volume":"8","author":"Prince","year":"2016","journal-title":"Alzheimer\u2019s Res. 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