{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:00:57Z","timestamp":1791198057784,"version":"4.1.0"},"reference-count":166,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Szecsei and Dhar families","award":["809194"],"award-info":[{"award-number":["809194"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Alzheimer\u2019s disease (AD) is a multifactorial neurodegenerative disorder characterized by interconnected pathological processes including mitochondrial dysfunction, oxidative stress, impaired autophagic processes, neuroinflammation, neuronal degeneration, and progressive functional decline. Natural health products (NHPs), coenzyme-Q10 (CoQ10) and Ashwagandha (Withania somnifera) (ASH), have been previously reported to possess antioxidant, anti-inflammatory, mitochondrial-supportive, neuroprotective, and neurotrophic properties. This work investigates the neuroprotective effects of a bioavailability-enhanced formulation, Ubisol-Q10 (UQ), and ethanolic ASH extract, combined as a \u201cTonic,\u201d across multiple domains of AD pathology. Methods: The effects of long-term administration were evaluated in male and female 5XFAD mice from 2.5 to 11 months of age. Longitudinal magnetic resonance imaging assessed hippocampal and white matter volumes, a frailty index assessed physiological resilience, Novel Object and Novel Location Recognition testing assessed spatial and non-spatial memory, while post-mortem Nissl, Golgi\u2013Cox, and immunofluorescence evaluated cellular density, dendritic morphology, amyloid pathology, neuroinflammation, autophagy-associated signaling, and astrocytic activity. Results: Across these measures, Tonic treatment preserved brain volumes, reduced amyloid pathology and inflammation, and modulated autophagy-associated pathways. Treatment also preserved dendritic architecture, frailty progression, and novelty-recognition behavior. Females demonstrated particularly pronounced preservation of white matter structure and increased dendritic density, whereas males showed strong modulation of inflammatory and autophagy-associated markers. Astrocytic immunoreactivity also demonstrated sex- and region-specific patterns, suggesting that glial responses may contribute differently to structural preservation in males and females. Conclusions: Together, these findings support that UQ + ASH may provide diverse protection against AD neurodegeneration. The observed sex-specific responses emphasize the importance of incorporating sex into preclinical evaluation of novel interventions for neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/nu18193270","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:02:27Z","timestamp":1791194547000},"page":"3270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multidimensional Neuroprotective Effects of Combined Ubisol-Q10 and Ashwagandha (Withania somnifera) in Male and Female 5XFAD Mice"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9186-1732","authenticated-orcid":false,"given":"Keanna","family":"Dube","sequence":"first","affiliation":[{"name":"Department of Integrative Biology, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3755-313X","authenticated-orcid":false,"given":"Alex","family":"Stoinescu","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6038-5104","authenticated-orcid":false,"given":"Julia","family":"Sadler","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Michelle","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2326-9189","authenticated-orcid":false,"given":"Natasha","family":"Malakoti-Negad","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Maira","family":"Chaudhry","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6704-6081","authenticated-orcid":false,"given":"Rohan","family":"Talukdar","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2787-2883","authenticated-orcid":false,"given":"Jerome","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7273-7154","authenticated-orcid":false,"given":"Siyaram","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nea\u021bu, M., Covaliu, A., Ioni\u021b\u0103, I., Jugurt, A., Davidescu, E.I., and Popescu, B.O. 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