1. Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease
- Author
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Xin Huang, Yihan Li, Christopher Fowler, James D. Doecke, Yen Ying Lim, Candace Drysdale, Vicky Zhang, Keunha Park, Brett Trounson, Kelly Pertile, Rebecca Rumble, John W. Pickering, Robert A. Rissman, Floyd Sarsoza, Sara Abdel‐Latif, Yong Lin, Vincent Doré, Victor Villemagne, Christopher C. Rowe, Jurgen Fripp, Ralph Martins, James S. Wiley, Paul Maruff, Jacobo E. Mintzer, Colin L. Masters, and Ben J. Gu
- Subjects
Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Abstract
Blood-based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at-risk individuals for therapeutic interventions.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.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.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.
- Published
- 2022