{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:42:23Z","timestamp":1763552543888,"version":"3.45.0"},"reference-count":59,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union-Next Generation EU","award":["PE_00000019"],"award-info":[{"award-number":["PE_00000019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) and osteoporosis frequently co-occur in the elderly; however, the pathophysiological link between these two diseases remains unclear. This study investigates skeletal alterations in a triple transgenic 3xTg-AD mouse model of AD (3xTg-AD), which harbors mutations in \u03b2-amyloid precursor protein (\u03b2APPSwe), presenilin-1 (PS1M146V), and tauP301L, and recapitulates key aspects of AD pathology, including age-dependent \u03b2-amyloid plaque accumulation and cognitive decline. To assess early skeletal changes, we analyzed femurs and tibiae of 2-month-old male non-Tg and 3xTg-AD mice (n = 9\/group) using micro-CT. Despite the absence of \u03b2-amyloid plaques at this stage, 3xTg-AD mice showed significant cortical bone loss, with reduced bone surface, periosteal and endosteal perimeters, total and cortical cross-sectional area, and polar moment of inertia. The 3-point-bending test confirmed compromised mechanical properties, including reduced maximum load-to-fracture and stiffness. Histological analyses highlighted an increased number of Empty Osteocyte Lacunae, reduced TRAP+ osteocytes, and an elevated number of osteoclasts; such evidence indicates impaired osteocyte function and increased bone resorption. These findings indicate that cortical bone loss and compromised mechanical properties occur before detectable neuropathological hallmarks in this AD model.<\/jats:p>","DOI":"10.3390\/cells14221816","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:17:27Z","timestamp":1763551047000},"page":"1816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cortical Bone Loss and Fragility in a 2-Month Triple Transgenic Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Giuseppina","family":"Storlino","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8099-3505","authenticated-orcid":false,"given":"Francesca","family":"Posa","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa Stefania","family":"Dell'Endice","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Piccolo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graziana","family":"Colaianni","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-806X","authenticated-orcid":false,"given":"Tommaso","family":"Cassano","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7121-5899","authenticated-orcid":false,"given":"Maria","family":"Grano","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-0247","authenticated-orcid":false,"given":"Giorgio","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Viale Pinto 1, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","unstructured":"London Alzheimer\u2019s Disease International (ADI) (2024, December 14). 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