Objective: To identify plasma biomarkers for the diag-nosis of Alzheimer disease (AD). Design: Baseline plasma screening of 151 multiplexed analytes combined with targeted biomarker and clinical pathology data. Setting: General community-based, prospective, lon-gitudinal study of aging. Participants: A total of 754 healthy individuals serv-ing as controls and 207 participants with AD from the Australian Imaging Biomarker and Lifestyle study (AIBL) cohort with identified biomarkers that were validated in 58 healthy controls and 112 individuals with AD from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. Results: A biomarker panel was identified that in-cluded markers significantly increased (cortisol, pancre-atic polypeptide, insulinlike growth factor binding pro-tein 2, 2 microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1, superox-ide dismutase, and homocysteine) and decreased (apo-lipoprotein E, epidermal growth factor receptor, hemo-globin, calcium, zinc, interleukin 17, and albumin) in AD. Cross-validated accuracy measures from the AIBL co-hort reached a mean (SD) of 85% (3.0%) for sensitivity and specificity and 93% (3.0) for the area under the re-ceiver operating characteristic curve . A second valida-tion using the ADNI cohort attained accuracy measures of 80% (3.0%) for sensitivity and specificity and 85% (3.0) for area under the receiver operating characteristic curve. Conclusions: This study identified a panel of plasma bio-markers that distinguish individuals with AD from cog-nitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis.