Longitudinal profiling of the aging plasma proteome to identify risk and resilience profiles in neurocognitive aging

Large-scale screening of the plasma proteome offers great potential for non-invasively predicting and understanding systemic contributory factors of age-related cognitive decline and dementia.

However, existing knowledge largely relies on cross-sectional data, limiting our understanding of true aging-related dynamics in the plasma proteome.

In our 3-year project, we will analyze 10-year intra-individual changes in 1500 plasma proteins in the longitudinal Betula study (n=568) as well as data from the large-scale cross-sectional UK Biobank (n=55,000 individuals; 2900 proteins).

Our unique longitudinal proteomic data will serve to identify and validate new sensitive proteomic markers for within-individual biological aging, find plasma proteins that track preclinical cognitive decline over a decade, and predict novel Alzheimer’s disease biomarker levels (plasma p-tau217) a decade in advance.

Additionally, we will uncover proteomic profiles of successfully aged individuals with preserved cognition over two decades.

The insights from this project will aid early detection of neurocognitive disorders, identify early upstream factors contributing to future accumulation of Alzheimer’s pathology, and inform the development of future treatments and interventions aiming to preserve and rejuvenate the aging brain.