Ontology highlight
ABSTRACT: 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.
SUBMITTER: Huang X
PROVIDER: S-EPMC10166765 | biostudies-literature | 2023 May
REPOSITORIES: biostudies-literature
Huang Xin X Li Yihan Y Fowler Christopher C Doecke James D JD Lim Yen Ying YY Drysdale Candace C Zhang Vicky V Park Keunha K Trounson Brett B Pertile Kelly K Rumble Rebecca R Pickering John W JW Rissman Robert A RA Sarsoza Floyd F Abdel-Latif Sara S Lin Yong Y Doré Vincent V Villemagne Victor V Rowe Christopher C CC Fripp Jurgen J Martins Ralph R Wiley James S JS Maruff Paul P Mintzer Jacobo E JE Masters Colin L CL Gu Ben J BJ
Alzheimer's & dementia : the journal of the Alzheimer's Association 20221109 5
<h4>Introduction</h4>Blood-based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at-risk individuals for therapeutic interventions.<h4>Methods</h4>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.<h4>Results</h4>We identified leukocyte markers differentially expressed in the patients with AD. Pathway anal ...[more]