Early detection of molecular signatures in amyloid conversion and cognitive decline through unbiased P2 plasma proteomics

Aging is the greatest risk factor for Alzheimer’s disease (AD), yet the biological pathways that distinguish healthy aging from pathological aging, which leads to neurodegeneration, remain poorly understood. There is a critical need for novel biomarkers that can detect the earliest changes in the disease process, particularly well before the onset of cognitive symptoms and preferably even before amyloid conversion that are currently diagnosed by blood/CSF Aβ42/Aβ40 ratio. Plasma represents an ideal biological matrix for novel biomarker discovery due to its ease of collection compared to CSF, its non-invasive nature, and its suitability for clinical biomarker discovery. To address this challenge, we developed a novel MS-based proteomics workflow to enable unbiased biomarker discovery.