SERS enables sensitive biomolecule detection by amplifying Raman signals at plasmonic “hot spots”, where the electric field is locally enhanced.[32, 33] It provides high‐dimensional molecular fingerprint data related to both the protein structure and quantity.[34, 35] Here, we report a non‐invasive and label‐free SERS‐based platform for detecting tau protein variants, which are key AD biomarkers, secreted from hCOs, thereby demonstrating the feasibility of the proposed in vitro approach for studying AD. This evidence concerns the gene MAPT and Alzheimer disease.