{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T18:27:06Z","timestamp":1777314426408,"version":"3.51.4"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Junk foods are typically low in essential nutrients, such as vitamins, minerals, and antioxidants. They are also loaded with trans fats and saturated fats, which can increase the level of triglycerides in the blood. High triglyceride levels can contribute to the development of non-alcoholic fatty liver disease (NAFLD), a condition where excess fat accumulates in the liver. A high intake of junk foods can lead to insulin resistance, a condition where the body\u2019s cells become less responsive to insulin. A diet lacking in nutrients and loaded with unwanted toxins can impair the liver\u2019s ability to detoxify harmful substances and damage its overall function. It is known that the regular consumption of junk food can be linked to memory impairment and cognitive decline. Several studies have shown that diets high in unhealthy fats, sugars, and processed foods can negatively impact brain health, including memory function. In this study, Wistar rats were used to model Late-Onset Alzheimer\u2019s Disease (LOAD), which was inspired by knowledge of the liver\u2013brain axis\u2019s role in causing dementia. The model mimicked junk-food-induced liver\u2013brain damage, and was developed by using the toxins d-galactosamine, ethanol and d-galactose. To begin with, the model rats demonstrated insulin resistance, a characteristic of LOAD patients. Glucose levels in both the brain and liver tissues were significantly elevated in the model, paralleling clinical findings in LOAD patients. High glucose levels in the brain lead to the increased production of advanced glycation end-products (AGEs), which, along with amyloid beta, harm neighbouring neurons. Histopathological analysis revealed deformed glial nodules, apoptotic neurons, and amyloid plaques in the brain section in the later stages of the disease. Simultaneously, the liver section displayed features of cirrhosis, including an effaced lobular architecture and the extravasation of red blood cells. Liver enzymes ALT, AST and ALP were consistently elevated with disease progression. Furthermore, immunohistochemistry confirmed the presence of amyloid precursor protein (APP) in the diseased brain. The positive expression of Hypoxia-Inducible Factor 3-Alpha (HIF3A) in the brain indicated hypoxic conditions, which is consistent with other LOAD studies. This model also exhibited damaged intestinal villi and excessive bowel and urinary incontinence, indicating malnutrition and a disturbed gut microbiome, which is also consistent with LOAD patients. Bioinformatics analysis on serum protein suggests a few affected molecular pathways, like the amyloid secretase pathway, androgen\/oestrogen\/progesterone biosynthesis, the apoptosis signalling pathway, the insulin\/IGF pathway-protein kinase B signalling cascade, the Metabotropic glutamate receptor group I pathway, the Wnt signalling pathway, etc. Behavioural analysis confirmed memory decline and the loss of muscle strength with disease progression. Overall, this rat model of LOAD sheds valuable light on LOAD pathology and highlights the potential link between liver dysfunction, particularly induced by the excessive consumption of junk food, and LOAD. This study contributes to a deeper understanding of the complex molecular mechanisms involved in LOAD, paving the way for new possibilities in therapeutic interventions.<\/jats:p>","DOI":"10.3390\/brainsci13101391","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T07:42:08Z","timestamp":1695973328000},"page":"1391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Connection between Chronic Liver Damage and Sporadic Alzheimer\u2019s Disease: Evidence and Insights from a Rat Model"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8404-9375","authenticated-orcid":false,"given":"Ruchi","family":"Jakhmola Mani","sequence":"first","affiliation":[{"name":"Proteomics and Translational Research Lab, Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida 201301, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nitu","family":"Dogra","sequence":"additional","affiliation":[{"name":"Proteomics and Translational Research Lab, Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida 201301, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1881-3566","authenticated-orcid":false,"given":"Deepshikha Pande","family":"Katare","sequence":"additional","affiliation":[{"name":"Proteomics and Translational Research Lab, Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida 201301, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"ref_1","unstructured":"Australia, D., Baker, S., and Banerjee, S. 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