Authors
Wilke M Post, Joanna Widomska, Egbert Oosterwijk, Ward De Witte, Dorien M Tiemessen, Cornelius J H M Klemann, Il Hyun Ruisch, Marieke J H Coenen, Dick A W Janssen, Frank Martens, Megan U Carnes, Jesse A Marks, Grier P Page, Holly E Richter, Rufus Cartwright, Vatche A Minassian, Laurent F Thomas, Anne H Skogholt, Signe N Stafne, Kristian Hveem, Kirsten B Kluivers, Geert Poelmans
Published in
International journal of molecular sciences. Volume 27. Issue 14. Jul 09, 2026. Epub Jul 09, 2026.
Abstract
Urgency urinary incontinence (UUI) and Alzheimer's disease (AD) are highly comorbid conditions in women, but the underlying molecular mechanisms are largely unknown. Therefore, we used network enrichment analyses and an elaborate literature search to integrate the most significant genes from four genome-wide association studies (GWASs) and other genetic, expression and functional evidence into a molecular landscape of female UUI. This molecular landscape centers around local, i.e., bladder-based, processing of the AD-associated amyloid precursor protein (APP). To further elucidate how APP processing is implicated in the comorbidity between UUI and AD, we conducted polygenic risk score (PRS)-based analyses, which showed that genetic risk factors associated with AD and a decreased amyloid beta 42/40 blood level ratio (also) contribute to UUI susceptibility. In conclusion, APP processing constitutes a putative molecular link between UUI and AD, adding further weight to their clinical comorbidity and having implications for the treatment (and prevention) of both traits.
PMID:
42511504
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.
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