Presenter of 1 Presentation
QUANTITATIVE DISSECTION OF HEALTHY AGING AND COGNITIVE DECLINE USING PROTEOFORM SIGNATURES FROM PAIRED CSF AND PLASMA
Abstract
Aims
While aging remains the most significant risk factor for Alzheimer’s disease (AD), the biological pathways that are altered in healthy aging vs. pathologic aging leading to neurodegeneration remain to be elucidated. Here, we seek to address this unmet need by applying a novel mass spectrometry-based discovery workflow. To unveil potential aging-related factors, we analyzed matched plasma and CSF proteomes between healthy aging and cognitive perturbations associated to the development of Alzheimer’s disease in its earliest phase.
Methods
Matched CSF and plasma samples were obtained from individuals at the same visit. Samples were collected from young control subjects (n= 53), subjects with mild cognitive impairment (MCI) (n = 40), age-matched healthy control subjects (n = 40) and subjects with autopsy-proven Alzheimer’s disease (n = 21). The plasma and CSF samples were subsequently processed to tryptic peptides and analyzed using a Thermo Scientific Orbitrap Exploris 480 equipped with a FAIMS Pro device. Clinical biomarkers (abeta40, abeta42, t-tau, ptau181) were assessed using the Lumipulse G1200 system.
Results
Using our optimized discovery workflow, we analyzed the above-described cohort of 133 matched plasma and CSF pairs and 21 additional CSF samples. This resulted in more than 50000 quantified peptides (associated with > 4000 proteins) in CSF and plasma. The correlative analyses of paired CSF and plasma samples allowed us to assess blood-brain barrier integrity in healthy and early pathological aging.
Conclusions
Harnessing the power of the latest advancement in mass spectrometry-based technique, we generated a comprehensive and quantitative map of proteoforms linked to healthy and pathological aging.