Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease
Alzheimer's and Dementia
School of Medical and Health Sciences / Centre of Excellence for Alzheimer's Disease Research and Care
National Health and Medical Research Council / Australian Research Council, Future Fellowship / Ministry of Science and Technology of China. Grant Number: SQ2018YFC200022 / Bethlehem Griffiths Research Foundation. Grant Number: BGRF1901 / Victorian Government's Operational Infrastructure / Florey Institute / NIH. Grant Numbers: AG058252, AG073979, AG051848
NHMRC Numbers: 1048082, 1061419, 1120095, 110178 ARC Number : FT120100581
http://purl.org/au-research/grants/nhmrc/1048082 http://purl.org/au-research/grants/nhmrc/1061419 http://purl.org/au-research/grants/nhmrc/1120095 http://purl.org/au-research/grants/arc/FT120100581
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.
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Huang, X., Li, Y., Fowler, C., Doecke, J. D., Lim, Y. Y., Drysdale, C., ... & Gu, B. J. (2022). Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease. Alzheimer's & Dementia. Advance online publication. https://doi.org/10.1002/alz.12813