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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2024

Open Access 01-12-2024 | Alzheimer's Disease | Research article

Adaptive immune changes associate with clinical progression of Alzheimer’s disease

Authors: Lynn van Olst, Alwin Kamermans, Sem Halters, Susanne M. A. van der Pol, Ernesto Rodriguez, Inge M. W. Verberk, Sanne G. S. Verberk, Danielle W. R. Wessels, Carla Rodriguez-Mogeda, Jan Verhoeff, Dorine Wouters, Jan Van den Bossche, Juan J. Garcia-Vallejo, Afina W. Lemstra, Maarten E. Witte, Wiesje M. van der Flier, Charlotte E. Teunissen, Helga E. de Vries

Published in: Molecular Neurodegeneration | Issue 1/2024

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Abstract

Background

Alzheimer’s disease (AD) is the most frequent cause of dementia. Recent evidence suggests the involvement of peripheral immune cells in the disease, but the underlying mechanisms remain unclear.

Methods

We comprehensively mapped peripheral immune changes in AD patients with mild cognitive impairment (MCI) or dementia compared to controls, using cytometry by time-of-flight (CyTOF).

Results

We found an adaptive immune signature in AD, and specifically highlight the accumulation of PD1+ CD57+ CD8+ T effector memory cells re-expressing CD45RA in the MCI stage of AD. In addition, several innate and adaptive immune cell subsets correlated to cerebrospinal fluid (CSF) biomarkers of AD neuropathology and measures for cognitive decline. Intriguingly, subsets of memory T and B cells were negatively associated with CSF biomarkers for tau pathology, neurodegeneration and neuroinflammation in AD patients. Lastly, we established the influence of the APOE ε4 allele on peripheral immunity.

Conclusions

Our findings illustrate significant peripheral immune alterations associated with both early and late clinical stages of AD, emphasizing the necessity for further investigation into how these changes influence underlying brain pathology.
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Metadata
Title
Adaptive immune changes associate with clinical progression of Alzheimer’s disease
Authors
Lynn van Olst
Alwin Kamermans
Sem Halters
Susanne M. A. van der Pol
Ernesto Rodriguez
Inge M. W. Verberk
Sanne G. S. Verberk
Danielle W. R. Wessels
Carla Rodriguez-Mogeda
Jan Verhoeff
Dorine Wouters
Jan Van den Bossche
Juan J. Garcia-Vallejo
Afina W. Lemstra
Maarten E. Witte
Wiesje M. van der Flier
Charlotte E. Teunissen
Helga E. de Vries
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2024
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-024-00726-8

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