In the present study, the quantitative metabolite data acquired in paired plasma and CSF samples combined with clinical diagnosis criteria, AD CSF biomarker data, and clinical metadata allowed us to identify and quantify metabolic alterations in AD and associate them with distinct AD pathologies (amyloid pathology (Aβ1–42), neuronal injury (tau), and tau hyperphosphorylation (pTau-181)), whilst deriving information on the most likely origin of these alterations (systemic or CNS). The gene discussed is MAPT; the disease is Alzheimer disease.