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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13024-024-00726-8.

Highlights

• Peripheral CD8 ⁺ TEMRA cells expressing markers associated with senescence accumulate in AD patients before dementia onset.

• Peripheral immune cells correlate with AD biomarkers, varying by clinical AD stage.

• APOE ε4 modifies peripheral immunity and its association with clinical AD measures.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13024-024-00726-8.

Related collections

Most cited references 85

Record: found
Abstract: found
Article: found

The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Guy M McKhann, David S. Knopman, Howard Chertkow … (2011)

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. Copyright © 2011. Published by Elsevier Inc.

0 comments Cited 2925 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Neuropathological stageing of Alzheimer-related changes

H Braak, E Braak (1991)

Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.

0 comments Cited 1940 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Marilyn Albert, Steven Dekosky, Dennis D Dickson … (2011)

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer's disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings. Copyright © 2011 The Alzheimer's Association. All rights reserved.

0 comments Cited 1850 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Lynn van Olst:

ORCID: http://orcid.org/0000-0001-7569-0470

l.vanolst@northwestern.edu

Journal

Journal ID (nlm-ta): Mol Neurodegener

Journal ID (iso-abbrev): Mol Neurodegener

Title: Molecular Neurodegeneration

Publisher: BioMed Central (London )

ISSN (Electronic): 1750-1326

Publication date (Electronic): 24 April 2024

Publication date PMC-release: 24 April 2024

Publication date Collection: 2024

Volume: 19

Electronic Location Identifier: 38

Affiliations

[1 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of Molecular Cell Biology and Immunology, , Amsterdam UMC Location Vrije Universiteit Amsterdam, ; De Boelelaan 1117, Amsterdam, the Netherlands

[2 ]Amsterdam Neuroscience, Neuroinfection & -Inflammation, ( https://ror.org/01x2d9f70) Amsterdam, the Netherlands

[3 ]Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, the Netherlands

[4 ]Cancer Center Amsterdam, Cancer Biology and Immunology, ( https://ror.org/0286p1c86) Amsterdam, the Netherlands

[5 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of Laboratory Medicine, Neurochemistry Laboratory, , Amsterdam UMC, Vrije Universiteit Amsterdam, ; De Boelelaan 1117, Amsterdam, the Netherlands

[6 ]Amsterdam Neuroscience, Neurodegeneration, ( https://ror.org/01x2d9f70) Amsterdam, the Netherlands

[7 ]Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, the Netherlands

[8 ]Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands

[9 ]Cancer Center Amsterdam, Imaging and Biomarkers, ( https://ror.org/0286p1c86) Amsterdam, the Netherlands

[10 ]GRID grid.16872.3a, ISNI 0000 0004 0435 165X, Department of Neurology, , Amsterdam UMC Location VUmc, Vrije Universiteit Amsterdam, ; Amsterdam, the Netherlands

[11 ]Amsterdam Institute for Infection and Immunity, Inflammatory Diseases, Amsterdam, the Netherlands

[12 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of Epidemiology & Data Science, , Amsterdam UMC Location VUmc, Vrije Universiteit Amsterdam, ; Amsterdam, the Netherlands

[13 ]Amsterdam Cardiovascular Sciences, Microcirculation, Amsterdam, the Netherlands

[14 ]Amsterdam Neuroscience, Neurovascular Disorders, ( https://ror.org/01x2d9f70) Amsterdam, the Netherlands

[15 ]Present address: The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, ( https://ror.org/000e0be47) Chicago, IL USA

Author information

Lynn van Olst http://orcid.org/0000-0001-7569-0470

Article

Publisher ID: 726

DOI: 10.1186/s13024-024-00726-8

PMC ID: 11044380

PubMed ID: 38658964

SO-VID: 1e0676f1-4b17-48c0-9332-e3aa2d71cf8f

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 25 July 2023

Date accepted : 29 March 2024

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100007601, Horizon 2020;

Award ID: 686009

Award Recipient : Helga E. de Vries

Funded by: FundRef http://dx.doi.org/10.13039/501100010969, Alzheimer Nederland;

Award ID: WE.03-2021-02

Award Recipient : Helga E. de Vries

Custom metadata

ScienceOpen disciplines: Neurosciences

Keywords: alzheimer’s disease,t cells,temra cells,adaptive immunity,apoe,neuroinflammation

Data availability:

ScienceOpen disciplines: Neurosciences

Keywords: alzheimer’s disease, t cells, temra cells, adaptive immunity, apoe, neuroinflammation

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

Read this article at

Abstract

Background

Methods

Results

Conclusions

Supplementary Information

Highlights

Supplementary Information

Related collections

Karger: Neurology and Neuroscience

Most cited references 85

The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Neuropathological stageing of Alzheimer-related changes

The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 212

Cited by 1

Most referenced authors 3,339