Associations of proteomic and epigenetic aging clocks with Alzheimer's disease phenotypes: An exploratory analysis

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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.

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