ArticlebioRxiv : the preprint server for biology2025
Alzheimer's Disease-Related Mutations in APP Influence Colorectal Tumor Formation in a Sex-Dependent Manner.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Cancer and Alzheimer's disease (AD) are major age-associated diseases. Numerous studies have indicated common mechanisms and biological interactions between these conditions. Furthermore, epidemiological data demonstrate negative correlations between several cancers and AD. Despite this, few studies have explored their mutual influence on pathological outcomes. We utilized a human APP mutant knock-in AD mouse model to investigate how familial mutations influence colorectal cancer development. Using a colitis-associated colorectal cancer model, APP mutations promoted colon tumor formation in male mice but inhibited it in female mice. Correspondingly, inflammatory changes were reduced in the colons of female mice. Transcriptome analysis revealed differential expression, particularly in the enrichment of neuronal marker, steroid hormone, and immune cell signaling pathways. Additionally, distinct macrophage subtypes and neuronal profiles were observed in the colons of male and female APP mutant mice. These findings provide the first elucidation of the sex-dependent effects of APP mutations on colon cancer formation.
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