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The study design included four groups, each consisting of six rats: the control group was fed regular chow, while groups 2 (HFD 2W), 3 (HFD 4W), and 4 (HFD 8W) were given a 60% HFD for 2, 4, and 8\u00a0weeks, respectively. A significant change in the latency to the platform in the water maze, a decrease in the percentage of successful cycles in the Y-maze, and a reduction in the percentage of time spent with the novel object were observed between the baseline and endpoint results in the HFD 4W and HFD 8W groups; notably, this was not the case in the control and HFD 2W groups. Consistent with the increased duration of HFD intake, marked damage to the cortical pyramidal cells as well as the mucosa of the ileum and colon was recorded. The optical density of amyloid deposition was significantly increased in the myenteric plexus before the cerebral cortex. In conclusion, increasing the duration of 60% HFD consumption was associated with significant deterioration of spatial and working memory, an increase in lipid profile, and amyloid deposition in the enteric nervous system, which began even before the observable involvement of the cerebral cortex.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s12035-025-05261-1","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T01:43:21Z","timestamp":1754617401000},"page":"16472-16488","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interruption of the Gut Integrity Contributes to Early Accumulation of Amyloid-\u03b2 in the Enteric Nervous System in Rats Supplemented with a High-Fat Diet"],"prefix":"10.1007","volume":"62","author":[{"given":"Zeinab","family":"Gawish","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maha","family":"Gamal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalia Azmy","family":"Elberry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esraa A.","family":"Hegazy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laila Ahmed","family":"Rashed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara Adel","family":"Hosny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa Nagi","family":"Mehesen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4250-0818","authenticated-orcid":false,"given":"Asmaa Mohammed","family":"ShamsEldeen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"5261_CR1","doi-asserted-by":"crossref","first-page":"1161521","DOI":"10.3389\/fendo.2023.1161521","volume":"14","author":"R Ruze","year":"2023","unstructured":"Ruze R, Liu T, Zou X et al (2023) Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments. 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