Associations of proteomic and epigenetic aging clocks with Alzheimer's disease phenotypes: An exploratory analysis
Abstract INTRODUCTION Proteomic aging clocks detect disease‐related systemic and organ‐specific changes and are easily accessible by minimally invasive blood draws. However, their potential in Alzheimer's disease (AD) assessment remains unestablished. METHODS We investigated associations of proteomic and epigenetic clocks with AD‐related blood‐based biomarkers and cognitive tests. Omics were generated from blood samples of 153 cognitively unimpaired individuals (average age 62 years); blood biomarkers and cognition were measured approximately nine years after. RESULTS Proteomic clocks explained up to 23% of variance in cognitive and biomarker measures not explained by epigenetics. Accelerated systemic and brain‐specific proteomic aging were linked to poorer cognition and higher levels of plasma neurofilament light chain. Exploratory interaction analyses suggested weaker proteomic aging‐cognition associations in individuals with higher genetic liability for diabetes. DISCUSSION Our study illustrates the potential of plasma proteomic clocks in detecting AD‐related phenotypes. However, co‐morbidities possibly constitute confounding factors, compromising the performance of proteomic aging models.