Transcriptional risk score for chronic kidney disease: relation to Alzheimer's disease.

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.