In conclusion, these findings establish a robust and high-resolution proteomic workflow for CSF analysis that not only confirms established biomarkers of canonical AD but also reveals distinct and reproducible molecular signatures that appear at early stages of the disease and well distinguish Aβ+/tau+ and Aβ+/tau-subtypes, paving the way for improved biomarker-based stratification of AD. Here, MAPT is linked to Alzheimer disease.