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There is also an abnormal buildup, misfolding and clumping of amyloid \u03b2 (A\u03b2). The present study aimed to explore the influence of the antihyperglycemic agent metformin on rats with AD-like symptoms, while also elucidating the intricate relationship between insulin resistance and AD. The rats were categorized into five groups: a control group, a saline-administered group, a metformin-treated group, AD-model rats, and AD-rats treated with a 200\u00a0mg\/kg dose of metformin. Cognitive impairment was rated using the classical labyrinth test. Moreover, serum biochemical parameters, encompassing glucose levels, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Glycated hemoglobin (HbA1c), lipid profile, kidney, and liver function, were evaluated. Additionally, oxidative, antioxidant, and neurotransmitter parameters were measured in hippocampus tissues. Also, the A\u03b2 and insulin receptor substrate 2 (IRS-2) were measured by immunoblotting. Besides hippocampal histopathology, glial fibrillary acidic protein (GFAP) and calretinin immunoreactivity were monitored. The study findings disclosed deficits in memory and learning capabilities among AD rats. Furthermore, AD-afflicted rats exhibited heightened glucose levels, elevated HOMA-IR and HbA1c values, alongside compromised liver, and kidney functions. Additionally, an upsurge in oxidative stress coincided with a notable reduction in the antioxidant system and neurotransmitters activities. The levels of A\u03b2 deposition increased, while IRS-2 expression subsided, accompanied by alterations in the hippocampal structure and neuronal damage. These changes were paralleled by an intensification in GFAP reactivity and a detracting in calretinin reactivity. Metformin was altogether able to move forward cognitive execution by means of bringing down oxidative stress and A\u03b2 conglomeration. Furthermore, metformin was able to improve neurotransmitters and insulin signals. AD, glucose impairment, and brain insulin resistance are completely interlinked, and future AD medications may be inspired by diabetic medication.<\/jats:p>","DOI":"10.1007\/s11011-024-01422-8","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T06:45:44Z","timestamp":1732517144000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Metformin effectively alleviates the symptoms of Alzheimer in rats by lowering amyloid \u03b2 deposition and enhancing the insulin signal"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3850-4258","authenticated-orcid":false,"given":"Hamed A.","family":"Abosharaf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5824-3676","authenticated-orcid":false,"given":"Yasmin","family":"Elsonbaty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9722-3603","authenticated-orcid":false,"given":"Ehab","family":"Tousson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-7542","authenticated-orcid":false,"given":"Tarek M.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"1422_CR1","doi-asserted-by":"publisher","first-page":"e13356","DOI":"10.1111\/jne.13356","volume":"36","author":"HA Abosharaf","year":"2024","unstructured":"Abosharaf HA, Elsonbaty Y, Tousson E, Mohamed TM (2024) Alzheimer\u2019s disease-related brain insulin resistance and the prospective therapeutic impact of metformin. 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