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The two main hypotheses regarding AD involve the accumulation of amyloid-\u03b2 (A\u03b2) forming plaques and the intracellular hyperphosphorylation of tau protein, leading to the formation of neurofibrillary tangles (NFT). These processes are accompanied by neuroinflammation and oxidative stress, and eventual neuronal death. While soy foods are widely recognized for their nutritional benefits, soybean pulp (okara), the residue left over from making tofu or soybean milk, is mostly discarded as kitchen waste, despite being rich in nutrients such as dietary fiber, protein, and isoflavones. This underutilized byproduct may serve as a valuable resource for functional food development and sustainable resource use. In this study, fermented soybean pulp (FS) demonstrated neuroprotective effects. In vitro, FS at concentrations of 0.001\u00a0\u00b5g\/mL and 0.01\u00a0\u00b5g\/mL significantly improved cell viability in A\u03b2-induced HT-22 cells and reduced lipid peroxidation. Further, in vivo oral administration of FS attenuated the cognitive deficits of 5\u2009\u00d7\u2009FAD mice, enhancing both short and long-term memory and reducing anxiety-like behaviors. Immunohistochemical analysis revealed that the FS-treated 5\u2009\u00d7\u2009FAD mice group significantly reduced hippocampal amyloid plaque accumulation and gliosis. FS also upregulated the expression levels of brain-derived neurotrophic factor (BDNF), PSD95, and synaptophysin, while preventing hippocampal neuronal loss. Mechanistically, FS may activate the Nrf2 antioxidant pathway and NF-\u03baB-mediated inflammation through the modulation of the Akt\/GSK3\u03b2 signaling axis in the hippocampus. These molecular actions likely contribute to increased antioxidant enzymes and suppressed neuroinflammatory responses. Overall, this study suggests that FS has therapeutic potential for alleviating cognitive and behavioral impairments in AD. Moreover, the repurposing of soybean pulp, which would otherwise be discarded, enhances its utilization value and supports sustainable green recycling.<\/jats:p>","DOI":"10.1007\/s12035-025-05191-y","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T03:53:50Z","timestamp":1752551630000},"page":"14121-14139","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fermented Soybean Pulp Alleviates Disease Progression of 5\u00d7FAD Model Mice"],"prefix":"10.1007","volume":"62","author":[{"given":"Chun-Yen","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta-Chun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Hsuan","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiu Mei","family":"Hsieh-Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"issue":"10284","key":"5191_CR1","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","volume":"397","author":"P Scheltens","year":"2021","unstructured":"Scheltens P, De Strooper B, Kivipelto M, Holstege H, Ch\u00e9telat G, Teunissen CE, Cummings J, van der Flier WM (2021) Alzheimer\u2019s disease. 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