The choroid plexus (ChP) is a critical brain barrier and producer of cerebrospinal fluid (CSF), playing a central role in maintaining brain homeostasis. Dr. Wyss-Coray and team will use in vivo labeling methods to identify newly synthesized ChP proteins in mice across age, APOE genotype, and Alzheimer’s disease (AD) models. By precisely mapping these proteins in CSF and plasma and linking them to cognitive outcomes and AD pathology in human samples, they aim to uncover ChP protein signatures of aging and Alzheimer’s risk.
They hypothesize that age-related changes in ChP protein production contribute to brain aging, cognitive decline, and neurodegeneration by disrupting key functions of the ChP over time and that profiling these proteins can reveal critical transitions in brain aging and identify pathways of vulnerability or resilience.
They will investigate this using three aims. In Aim 1, they will identify and quantify ChP proteins in mouse models of aging and AD to define age- and genotype-specific changes in protein synthesis. In Aim 2, they will characterize how these ChP-derived proteins appear in CSF and plasma and associate with cognitive function and AD pathology in human samples. In Aim 3, they will integrate ChP proteomic data with transcriptomic, lipidomic, and genetic datasets and complement these with findings from neuronal cultures and other multi-omic analyses to build a comprehensive systems-level view of ChP contributions to brain aging and AD.
By integrating these proteomic data with transcriptomic, lipidomic, and genetic datasets, and complementing with findings from neuronal cultures and other multi-omic analyses, they will create a systems-level view of ChP contributions to brain aging and AD. Validated signatures will be shared with Brain Aging Consortium members for independent validation and functional studies across collaborating labs.
