{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:13:17Z","timestamp":1788894797588,"version":"build-2803163510"},"reference-count":90,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008792","name":"Universidad de Magallanes","doi-asserted-by":"crossref","award":["40042452-0"],"award-info":[{"award-number":["40042452-0"]}],"id":[{"id":"10.13039\/501100008792","id-type":"DOI","asserted-by":"crossref"}]},{"award":["40042452-0"],"award-info":[{"award-number":["40042452-0"]}],"id":[{"id":"https:\/\/ror.org\/049784n50","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Emerging evidence implicates metabolic dysfunction as a key contributor to Alzheimer\u2019s disease (AD) pathogenesis. Fructose, a major component of modern diets, promotes systemic metabolic alterations; however, its direct impact on AD-related brain dysfunction remains poorly defined. Here, we investigated the effects of short-term fructose consumption on systemic metabolism, brain glucose handling, and cognitive performance in APP\/PS1 transgenic mice. Six-month-old asymptomatic male mice received 15% fructose in drinking water for eight weeks, while controls received plain water. Fructose-fed APP\/PS1 mice developed metabolic alterations consistent with early metabolic syndrome, including increased fasting glucose and dyslipidemia. These changes were accompanied by reduced cerebral glucose utilization, increased A\u03b242 accumulation, and impaired cognitive performance. In parallel, fructose intake enhanced neuroinflammatory markers, suggesting a coordinated disruption of metabolic and inflammatory pathways in the brain. Collectively, these findings support the idea that fructose consumption may exacerbate Alzheimer-like alterations linking systemic metabolic dysfunction to impaired brain glucose metabolism and neuroinflammation. This study provides mechanistic evidence supporting a role for dietary fructose as a modifiable risk factor in AD vulnerability.<\/jats:p>","DOI":"10.3390\/ijms27094113","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T07:57:29Z","timestamp":1777967849000},"page":"4113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fructose Intake Is Associated with Brain Metabolic Reprogramming and Exacerbation of Alzheimer-like Alterations in APP\/PS1 Mice"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1160-8463","authenticated-orcid":false,"given":"Paulina","family":"Ormazabal","sequence":"first","affiliation":[{"name":"Facultad de Ciencias para el Cuidado de la Salud, Universidad San Sebasti\u00e1n, Lota 2465, Providencia, Santiago 8420524, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio","family":"\u00d3rdenes-Constenla","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Universidad San Sebasti\u00e1n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Gherardelli","sequence":"additional","affiliation":[{"name":"Mitchell Center for Alzheimer\u2019s Disease and Related Brain Disorders, Department of Neurology, University of Texas McGovern Medical School, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianela","family":"Bast\u00edas-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III (ISCIII), E-28029 Madrid, Spain"},{"name":"N\u00facleo de Investigaci\u00f3n en Nutrici\u00f3n y Ciencias Alimentarias (NINCAL), Facultad de Salud y Ciencias Sociales, Universidad de Las Am\u00e9ricas, Santiago 1530000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Brito-Valenzuela","sequence":"additional","affiliation":[{"name":"Departamento de Obstetricia y Puericultura, Facultad de Medicina, Universidad de Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-1708","authenticated-orcid":false,"given":"Marcelo","family":"Flores-Opazo","sequence":"additional","affiliation":[{"name":"Musculoskeletal Rehabilitation Laboratory, Institute Exercise and Rehabilitation Sciences (ICER), Universidad Andr\u00e9s Bello, Campus Casona, Las Condes, 7550000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nibaldo C.","family":"Inestrosa","sequence":"additional","affiliation":[{"name":"Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Escuela de Medicina, Universidad de Magallanes, Punta Arenas 6200000, Chile"},{"name":"Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Av. Bernardo O\u2019Higgins 340, Santiago 7820436, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7796-8982","authenticated-orcid":false,"given":"Pedro","family":"Cisternas","sequence":"additional","affiliation":[{"name":"N\u00facleo de Investigaci\u00f3n en Nutrici\u00f3n y Ciencias Alimentarias (NINCAL), Facultad de Salud y Ciencias Sociales, Universidad de Las Am\u00e9ricas, Santiago 1530000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1177\/1533317509348208","article-title":"Obesity and alzheimer\u2019s disease: A link between body weight and cognitive function in old age","volume":"24","author":"Naderali","year":"2009","journal-title":"Am. J. Alzheimer\u2019s Dis. 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