{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T00:19:34Z","timestamp":1794615574083,"version":"4.9.1"},"reference-count":53,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>VEXAS syndrome and Alzheimer\u2019s disease (AD), though distinct in clinical manifestations, share overlapping pathophysiological mechanisms, including systemic inflammation, protein misfolding, and vascular dysfunction. VEXAS syndrome, a rare autoinflammatory disorder characterized by somatic UBA1 mutations, systemic inflammation, and hematologic abnormalities, presents primarily in older males. Meanwhile, AD, the leading cause of dementia, involves progressive neurodegeneration driven by amyloid-beta plaques, tau tangles, and chronic neuroinflammation. This article explores potential connections between the two conditions, focusing on inflammation, neurovascular changes and cellular stress. Systemic inflammation observed in VEXAS syndrome may potentiate neuroinflammatory processes in Alzheimer\u2019s disease (AD), as circulating proinflammatory cytokines have the capacity to cross the blood\u2013brain barrier (BBB), thereby inducing glial activation and promoting neuroinflammation. Additionally, coexisting vascular dysfunctions characteristic of both conditions may synergistically contribute to accelerated cognitive decline. Both conditions involve disruption of the ubiquitin\u2013proteasome system, with UBA1 mutations being specific to VEXAS. Given the established role of UBA1 in maintaining neuronal homeostasis, investigating the overlapping and distinct molecular mechanisms may provide valuable insights into their pathophysiology. The review underscores the need for further research to elucidate these links and improve therapeutic strategies, especially for individuals affected by both disorders.<\/jats:p>","DOI":"10.3390\/brainsci15060573","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T08:12:47Z","timestamp":1748419967000},"page":"573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["VEXAS Syndrome and Alzheimer\u2019s Disease\u2014Are There Connections?"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3606-8756","authenticated-orcid":false,"given":"Aleksandra","family":"Sowa","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1955-6512","authenticated-orcid":false,"given":"Marta","family":"Malicka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8861-4910","authenticated-orcid":false,"given":"Magdalena","family":"Biernacka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Aleksander","family":"Besz\u0142ej","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Leszek","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1056\/NEJMoa2026834","article-title":"Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease","volume":"383","author":"Beck","year":"2020","journal-title":"N. 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