ArticleJournal of neuroinflammation2026
Selective vulnerability of the aging cholinergic system to amyloid pathology revealed by induced APP overexpression.
Article in Journal of neuroinflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
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7 authors.
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Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid beta (Aβ) accumulation, tau pathology, and cognitive decline, with aging as the primary risk factor. To investigate whether age influences susceptibility to Aβ toxicity, we used a tetracycline-inducible mouse model expressing a mutant human APP transgene (APPSweInd) and initiated expression during either mid-age (6-18 months) or old age (12-24 months). After one year of transgene activation, we assessed behavior, amyloid pathology, inflammation, autophagy, and brain gene expression compared to age-matched controls. Although APP expression, Aβ deposition, inflammatory markers, and autophagic flux were comparable between age groups, aged APP-expressing mice displayed cognitive impairments, hyperactivity, and motor deficits that were absent in their younger counterparts. Transcriptomic analysis revealed selective downregulation of cholinergic system genes specifically in the aged APP-induced group, validated at RNA and protein levels. No changes were observed in markers of other neuronal cell types, indicating a targeted cholinergic vulnerability. These findings suggest that age enhances the brain's susceptibility to Aβ toxicity, particularly affecting the cholinergic system, rather than amplifying amyloid burden itself. This inducible model provides a relevant platform to study the interaction between aging and Aβ pathology and may help identify age-related factors contributing to AD progression.
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