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Cited by 74Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

Neuroimmune contributions to Alzheimer’s disease: a focus on human data

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Haage, Verena, De Jager, Philip L.·2022·Molecular Psychiatry
DOI 10.1038/s41380-022-01637-0PMC PMC9168642
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Abstract

The past decade has seen the convergence of a series of new insights that arose from genetic and systems analyses of Alzheimer's disease (AD) with a wealth of epidemiological data from a variety of fields; this resulted in renewed interest in immune responses as important, potentially causal components of AD. Here, we focus primarily on a review of human data which has recently yielded a set of robust, reproducible results that exist in a much larger universe of conflicting reports stemming from small studies with important limitations in their study design. Thus, we are at an important crossroads in efforts to first understand at which step of the long, multiphasic course of AD a given immune response may play a causal role and then modulate this response to slow or block the pathophysiology of AD. We have a wealth of new experimental tools, analysis methods, and capacity to sample human participants at large scale longitudinally; these resources, when coupled to a foundation of reproducible results and novel study designs, will enable us to monitor human immune function in the CNS at the level of complexity that is required while simultaneously capturing the state of the peripheral immune system. This integration of peripheral and central perturbations in immune responses results in pathologic responses in the central nervous system parenchyma where specialized cellular microenvironments composed of multiple cell subtypes respond to these immune perturbations as well as to environmental exposures, comorbidities and the impact of the advancing life course. Here, we offer an overview that seeks to illustrate the large number of interconnecting factors that ultimately yield the neuroimmune component of AD.

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  • Recruitment of adaptive immune cells, particularly T and B lymphocytes, can exacerbate neurodegeneration through sustained cytokine production.

    “In parallel, recruitment of adaptive immune cells—particularly T and B lymphocytes—can further exacerbate neurodegeneration through sustained cytokine production despite their initial roles in aggregate clearance [37–41].”

    From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [37]

    The T Cells section reports T-cell infiltration in AD brains and suggests that CD8+ T cells might contribute to neuronal dysfunction; it also discusses effects on T-cell cytokine secretion. But it says the role of T cells in AD remains unclear. The cited passages do not establish that recruited T and B lymphocytes exacerbate neurodegeneration through sustained cytokine production, or that they initially clear aggregates. Page numbers are unavailable in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The enrichment of prioritized proteins in microglia and immune pathways supports a strong immunological role in AD, including TREM2, CD33, and IL34.

    “supporting a strong immunological role in AD93–95 including TREM27,96, CD33, and IL34.”

    From Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease (2024) · cites this paper as [95]

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Sorted by citations

Authors
Haage, V., & De Jager, P. L.
Affiliations
Columbia University Irving Medical Center (US)
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2022-06-06
Volume
27
Issue
8
Pages
3164-3181
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-022-01637-0
PMC
PMC9168642
OpenAlex
W4281735954
Cited by
74
References
60
Citations by year
2026: 13 · 2025: 19 · 2024: 23 · 2023: 12 · 2022: 7
FWCI
1.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, neuroinflammation, neuroimmune interactions, peripheral immune system, central nervous system immune response, pathogenesis, comorbidities, environmental exposure
MeSH terms
Alzheimer Disease, Central Nervous System, Humans, Research Design, Causality

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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