Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease.
Alzheimer's disease
CD11c
CD163
CD59
CD91
ROC curve
complement system
innate phagocytosis
leukocyte biomarker
peripheral immune response
receptor for advanced glycation end products (RAGE)
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
24
08
2022
received:
29
03
2022
accepted:
02
09
2022
pmc-release:
01
05
2024
medline:
15
5
2023
pubmed:
10
11
2022
entrez:
9
11
2022
Statut:
ppublish
Résumé
Blood-based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at-risk individuals for therapeutic interventions. 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. 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. 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.
Identifiants
pubmed: 36349985
doi: 10.1002/alz.12813
pmc: PMC10166765
mid: NIHMS1840176
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2084-2094Subventions
Organisme : NIA NIH HHS
ID : R01 AG058252
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062429
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG051848
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG010483
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG073979
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG057437
Pays : United States
Informations de copyright
© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
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