Cross‐Platform Synaptic Network Analysis of Alzheimer’s Disease Contextualizes Proteomic Targets for Functional Validation

Cognitive decline in Alzheimer’s disease (AD) correlates well with the extent of tau pathology and synapse or dendritic spine loss. Thus, studying synaptic processes may aid in the identification of new therapeutic targets that limit cognitive decline. The entorhinal cortex (EC) is an initial site of tau tangle formation, from which tau can propagate to other brain regions through synaptic connections. We developed a pipeline whereby dendritic spine density and morphology as well as synaptic tau measurements from the EC were incorporated into a synaptic proteomic network to identify mechanisms of synaptic pathology in AD patients.