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.