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We previously showed that osteoblast\u2010specific expression of APP\n                    <jats:sub>swe<\/jats:sub>\n                    induces bone loss, glial activation, and behavioral deficits, suggesting a bone\u2010to\u2010brain signaling axis. Here, we identify an altered skull bone marrow (SBM)\u2010to\u2010brain axis in AD. Early SBM changes, including reduced cellularity, increased density, and expanded vascular channels to the meninges, occur in multiple APP\n                    <jats:sub>swe<\/jats:sub>\n                    mouse models. These vascular changes facilitate migration of SBM\u2010derived myeloid cells into the meninges and cortex, improving cerebral blood flow (CBF) and slowing cognitive decline. Notably, these effects are age\u2010dependent, emerging at 6 months but diminishing by 12 months. Enhancing this axis via bone marrow transplantation improves CBF and cognitive function in aged mice, whereas disrupting it through osteoblastic deletion of ATP6AP2 impairs both. Together, these findings reveal a previously unrecognized SBM\u2010to\u2010brain axis that regulates immune, vascular, and cognitive functions, highlighting systemic contributions to AD pathogenesis.\n                  <\/jats:p>","DOI":"10.1002\/advs.75622","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T18:04:17Z","timestamp":1778436257000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Skull Bone Marrow\u2010to\u2010Brain Axis Links Osteoblastic Activity to Myeloid Cell Trafficking, Cerebral Blood Flow, and Cognition in Alzheimer's Progression"],"prefix":"10.1002","volume":"13","author":[{"given":"Lei","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Neurosciences School of Medicine Case Western Reserve University  Cleveland Ohio 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