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Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease.
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; Gu, Ben J.
Affiliation
  • Huang X; The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
  • Li Y; The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
  • Fowler C; The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
  • Doecke JD; The Australian e-Health Research Centre, CSIRO, Brisbane, Queensland, Australia.
  • Lim YY; Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
  • Drysdale C; The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
  • Zhang V; The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
  • Park K; The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
  • Trounson B; The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
  • Pertile K; The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
  • Rumble R; The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
  • Pickering JW; Department of Medicine, University of Otago, New Zealand and Department of Emergency Medicine, Christchurch Hospital, Christchurch, New Zealand.
  • Rissman RA; Department of Neurosciences, University of California, San Diego, California, USA.
  • Sarsoza F; Department of Neurosciences, University of California, San Diego, California, USA.
  • Abdel-Latif S; Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA.
  • Lin Y; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
  • Doré V; The Australian e-Health Research Centre, CSIRO, Brisbane, Queensland, Australia.
  • Villemagne V; Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia, and Department of Medicine, the University of Melbourne, Melbourne, Australia.
  • Rowe CC; Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia, and Department of Medicine, the University of Melbourne, Melbourne, Australia.
  • Fripp J; Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia, and Department of Medicine, the University of Melbourne, Melbourne, Australia.
  • Martins R; The Australian e-Health Research Centre, CSIRO, Brisbane, Queensland, Australia.
  • Wiley JS; Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
  • Maruff P; The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
  • Mintzer JE; The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
  • Masters CL; CogState Ltd., Melbourne, Victoria, Australia.
  • Gu BJ; NeuroQuest, Inc., Medical University of South Carolina, South Carolina, USA.
Alzheimers Dement ; 19(5): 2084-2094, 2023 05.
Article de En | MEDLINE | ID: mdl-36349985
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 Aß clearance. A proposed panel including four leukocyte markers - CD11c, CD59, CD91, and CD163 - predicts patients' PET Aß 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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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Maladie d'Alzheimer Type d'étude: Prognostic_studies Limites: Humans Langue: En Journal: Alzheimers Dement Année: 2023 Type de document: Article Pays d'affiliation: Australie
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Maladie d'Alzheimer Type d'étude: Prognostic_studies Limites: Humans Langue: En Journal: Alzheimers Dement Année: 2023 Type de document: Article Pays d'affiliation: Australie