VEXAS Syndrome and Alzheimer’s Disease—Are There Connections?
VEXAS syndrome and Alzheimer’s 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 muta...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3425/15/6/573 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850156553726853120 |
|---|---|
| author | Aleksandra Sowa Marta Malicka Magdalena Biernacka Jan Aleksander Beszłej Jerzy Leszek |
| author_facet | Aleksandra Sowa Marta Malicka Magdalena Biernacka Jan Aleksander Beszłej Jerzy Leszek |
| author_sort | Aleksandra Sowa |
| collection | DOAJ |
| description | VEXAS syndrome and Alzheimer’s 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’s disease (AD), as circulating proinflammatory cytokines have the capacity to cross the blood–brain 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–proteasome 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. |
| format | Article |
| id | doaj-art-ec0ba57fcc6142d9bb29e9d822c8097d |
| institution | OA Journals |
| issn | 2076-3425 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj-art-ec0ba57fcc6142d9bb29e9d822c8097d2025-08-20T02:24:29ZengMDPI AGBrain Sciences2076-34252025-05-0115657310.3390/brainsci15060573VEXAS Syndrome and Alzheimer’s Disease—Are There Connections?Aleksandra Sowa0Marta Malicka1Magdalena Biernacka2Jan Aleksander Beszłej3Jerzy Leszek4Department of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, PolandDepartment of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, PolandDepartment of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, PolandDepartment of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, PolandDepartment of Psychiatry, Wroclaw Medical University, 50-367 Wroclaw, PolandVEXAS syndrome and Alzheimer’s 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’s disease (AD), as circulating proinflammatory cytokines have the capacity to cross the blood–brain 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–proteasome 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.https://www.mdpi.com/2076-3425/15/6/573Alzheimer’s diseaseVEXASinflammationdementianeurodegenerationcognitive decline |
| spellingShingle | Aleksandra Sowa Marta Malicka Magdalena Biernacka Jan Aleksander Beszłej Jerzy Leszek VEXAS Syndrome and Alzheimer’s Disease—Are There Connections? Brain Sciences Alzheimer’s disease VEXAS inflammation dementia neurodegeneration cognitive decline |
| title | VEXAS Syndrome and Alzheimer’s Disease—Are There Connections? |
| title_full | VEXAS Syndrome and Alzheimer’s Disease—Are There Connections? |
| title_fullStr | VEXAS Syndrome and Alzheimer’s Disease—Are There Connections? |
| title_full_unstemmed | VEXAS Syndrome and Alzheimer’s Disease—Are There Connections? |
| title_short | VEXAS Syndrome and Alzheimer’s Disease—Are There Connections? |
| title_sort | vexas syndrome and alzheimer s disease are there connections |
| topic | Alzheimer’s disease VEXAS inflammation dementia neurodegeneration cognitive decline |
| url | https://www.mdpi.com/2076-3425/15/6/573 |
| work_keys_str_mv | AT aleksandrasowa vexassyndromeandalzheimersdiseasearethereconnections AT martamalicka vexassyndromeandalzheimersdiseasearethereconnections AT magdalenabiernacka vexassyndromeandalzheimersdiseasearethereconnections AT janaleksanderbeszłej vexassyndromeandalzheimersdiseasearethereconnections AT jerzyleszek vexassyndromeandalzheimersdiseasearethereconnections |