Cindy David Sarmento, Gabin Drouard, Toni T Saari, Aino Aaltonen, Aino Heikkinen, Mikaela Hukkanen, Teemu Palviainen, Sanna-Kaisa Herukka, Tarja Kokkola, Sari Kärkkäinen, FinnGen, Aarno Palotie, Valtteri Julkunen, Heiko Runz, Jaakko Kaprio, Miina Ollikainen, Eero Vuoksimaa
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.
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.