Abstract
INTRODUCTION
Although Alzheimer’s disease (AD) is prevalent in individuals with chronic kidney disease (CKD), the mechanistic link remains unclear. We assessed the impact of CKD transcriptional risk on AD endophenotypes.
METHODS
We calculated the CKD transcriptional risk score (CKD-TRS) using blood transcriptomes from the Alzheimer’s Disease Neuroimaging Initiative (n = 661) and AddNeuroMerge (n = 665) and brain transcriptomes from the Religious Orders Study and Rush Memory and Aging Project (n = 622) and analyzed its associations with longitudinal cognition, brain volume, amyloidopathy, tauopathy, and mediation effects.
RESULTS
Higher blood-based CKD-TRS was associated with accelerated cognitive decline, rapid temporal cortical atrophy, and faster amyloid accumulation. Brain-based CKD-TRS was similarly linked to faster cognitive decline and greater amyloid burden, with amyloidopathy partially mediating the CKD-TRS–cognition association.
DISCUSSION
Our findings suggest that CKD-TRS is associated with progressive neurodegeneration in AD, mediated by amyloidopathy, highlighting a shared molecular pathway.
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This post is Copyright: | September 24, 2026
Neuro-Dementia