Importantly, we provide the first insight into neuronal alterations that coincide with incipient tau pathology: the signaling pathway for Reelin, recently shown to be a major AD resilience gene is dysregulated in ECII neurons, while the secreted synaptic organizer molecules NPTX2 and CBLN4, emerging AD biomarkers, are downregulated in surrounding neurons. Here, RELN is linked to Alzheimer disease.