Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease

Introduction Blood‐based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at‐risk individuals for therapeutic interventions. Methods In three stages, a total of 34 leukocyte antigens were examined by flow cytometry immunophenotyping. Data were analyzed by logistic regression and receiver operating characteristic (ROC) analyses. Results We identified leukocyte markers differentially expressed in the patients with AD. Pathway analysis revealed a complex network involving upregulation of complement inhibition and downregulation of cargo receptor activity and Aβ clearance. A proposed panel including four leukocyte markers – CD11c, CD59, CD91, and CD163 – predicts patients’ PET Aβ status with an area under the curve (AUC) of 0.93 (0.88 to 0.97). CD163 was the top performer in preclinical models. These findings have been validated in two independent cohorts. Conclusion Our finding of changes on peripheral leukocyte surface antigens in AD implicates the deficit in innate immunity. Leukocyte‐based biomarkers prove to be both sensitive and practical for AD screening and diagnosis.