Document Type
Journal Article
Publication Title
Alzheimer's and Dementia
PubMed ID
36349985
Publisher
Wiley
School
School of Medical and Health Sciences / Centre of Excellence for Alzheimer's Disease Research and Care
RAS ID
54152
Funders
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
Grant Number
NHMRC Numbers: 1048082, 1061419, 1120095, 110178ARC Number : FT120100581
Grant Link
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
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.
DOI
10.1002/alz.12813
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
Huang, X., Li, Y., Fowler, C., Doecke, J. D., Lim, Y. Y., Drysdale, C., ... & Gu, B. J. (2023). Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease. Alzheimer's & Dementia, 19(5), 2084-2094.
https://doi.org/10.1002/alz.12813