Alzheimer & Dementia: Changes in peripheral leukocyte surface antigens suggest innate immunodeficiency in sporadic Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment, functional degeneration, and dementia
.
Pathologically, AD is defined as amyloid plaques and nerve fiber tangles
due to the accumulation of 42-amino acid amyloid β peptide (Aβ42) and phosphorylated tau protein.
The diagnosis and prognosis of blood-based sporadic AD is important
in determining populations at high risk for therapeutic interventions.

Currently, the diagnosis of AD relies on clinical evaluation and information from imaging and biofluid markers with the aim of detecting the presence of
Aβ42 and phosphorylated tau proteins.
Scholars from the University of Melbourne and Fudan University jointly examined a total of 34 leukocyte antigens
by flow cytometry immunophenotyping.
Analysis of data by logistic regression and recipient operating characteristics (ROC) analysis identified innate immunodeficiencies
suggestive of sporadic Alzheimer's disease by leukocyte surface biomarkers.

It was found that there were differences in the expression of white blood cell markers in AD patients
.
Pathway analysis shows a complex network involving upregulation of complement inhibition and downregulation of cargo receptor activity as well as Aβ clearance
.
A proposed panel that includes four leukocyte markers — CD11c, CD59, CD91 and CD163 — could predict a patient's PET Aβ status with an area under the curve (AUC) of 0.
93 (0.
88-0.
97).

Among them, CD163 is the best
performing in preclinical models.
These findings have been validated
in two separate cohorts.

In summary, the study found that changes in peripheral leukocytes surface antigen in AD patients were associated with
the loss of innate immunity.
Leukocytes-based biomarkers have proven to be both sensitive and practical
for screening and diagnosing AD.

References:

Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease.
https://doi.
org/10.
1002/alz.
12813