1. Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease
- Author
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Huang, Xin, Li, Yihan, Fowler, Christopher, Doecke, James D, Lim, Yen Ying, Drysdale, Candace, Zhang, Vicky, Park, Keunha, Trounson, Brett, Pertile, Kelly, Rumble, Rebecca, Pickering, John W, Rissman, Robert A, Sarsoza, Floyd, Abdel‐Latif, Sara, Lin, Yong, Doré, Vincent, Villemagne, Victor, Rowe, Christopher C, Fripp, Jurgen, Martins, Ralph, Wiley, James S, Maruff, Paul, Mintzer, Jacobo E, Masters, Colin L, and Gu, Ben J
- Subjects
Biomedical and Clinical Sciences ,Biological Psychology ,Clinical Sciences ,Neurosciences ,Psychology ,Neurodegenerative ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Alzheimer's Disease ,Brain Disorders ,Acquired Cognitive Impairment ,Dementia ,Aging ,2.1 Biological and endogenous factors ,Aetiology ,Detection ,screening and diagnosis ,4.1 Discovery and preclinical testing of markers and technologies ,Humans ,Alzheimer Disease ,Amyloid beta-Peptides ,Biomarkers ,Leukocytes ,Immunity ,Innate ,Alzheimer's disease ,CD11c ,CD163 ,CD59 ,CD91 ,complement system ,innate phagocytosis ,leukocyte biomarker ,peripheral immune response ,receptor for advanced glycation end products ,ROC curve ,Geriatrics ,Clinical sciences ,Biological psychology - Abstract
IntroductionBlood-based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at-risk individuals for therapeutic interventions.MethodsIn 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.ResultsWe 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.ConclusionOur 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
- 2023