Cited by 2,134Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Immune attack: the role of inflammation in Alzheimer disease

Heppner, Frank L., Ransohoff, Richard M., Becher, Burkhard·2015·Nature Reviews Neuroscience

Abstract

The past two decades of research into the pathogenesis of Alzheimer disease (AD) have been driven largely by the amyloid hypothesis; the neuroinflammation that is associated with AD has been assumed to be merely a response to pathophysiological events. However, new data from preclinical and clinical studies have established that immune system-mediated actions in fact contribute to and drive AD pathogenesis. These insights have suggested both novel and well-defined potential therapeutic targets for AD, including microglia and several cytokines. In addition, as inflammation in AD primarily concerns the innate immune system - unlike in 'typical' neuroinflammatory diseases such as multiple sclerosis and encephalitides - the concept of neuroinflammation in AD may need refinement.

Integrity signals

Registry

Crossref · 10.1038/nrn3880

Cites

218 of 218 references verified0 citation errors · 0 not checkable

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  • In brain tissue from human Alzheimer's disease patients, microglia display the morphology and gene expression profile characteristic of an activated cell state and cluster around β-amyloid plaques.

    “In brain tissue from human AD patients, microglia display the morphology (Heppner et al., 2015) and gene expression profile (Gjoneska et al., 2015; Mathys et al., 2019) characteristic of an activated cell state and cluster around β-amyloid plaques.”
  • Immune molecules IL-1β, IL-6 and CCL2 are produced by brain endothelial cells against Aβ plaque.

    “Immune molecules like IL-1β, IL-6 and CCL2 are produced by brain endothelial cells against Aβ plaque [18].”
  • Glial activation indicates pro-inflammatory changes commonly seen in Alzheimer's disease brains.

    “glial activation is an indication of pro-inflammatory changes that is commonly found in AD brains”

    From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [98]

  • In AD brains, microglia surrounding amyloid plaques have activated amoeboid morphology with enlarged soma and retracted processes.

    “In AD brains, microglia surrounding amyloid plaques display activated amoeboid morphologies with enlarged soma and retracted processes, indicating microglial response to protein accumulation or increased inflammatory mediators [41, 46-48].”
  • This morphology indicates microglial response to protein accumulation or increased inflammatory mediators.

    “indicating microglial response to protein accumulation or increased inflammatory mediators [41, 46-48].”

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Authors
Heppner, F. L., Ransohoff, R. M., & Becher, B.
Affiliations
  • NeuroCure Cluster of Excellence (DE)
  • Biogen (United States) (US)
  • University of Zurich (CH)
Corresponding author
  • Heppner, Frank L.
  • Ransohoff, Richard M.
  • Becher, Burkhard
Venue
Nature Reviews Neuroscience
Published
2015-05-20
Volume
16
Issue
6
Pages
358-372
ISSN
  • 1471-003X (ISSN-L)
  • 1471-0048
OpenAlex
W1841850981
Cited by
2,134
References
220
Citations by year
2026: 121 · 2025: 157 · 2024: 166 · 2023: 173 · 2022: 211 · 2021: 264 · 2020: 221 · 2019: 192 · 2018: 225 · 2017: 205 · 2016: 153 · 2015: 43
FWCI
16.69
Type
journal article
Language
en
Open access
closed
Locations
  • Nature reviews. Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
Alzheimer's disease, neuroinflammation, innate immunity, microglia, cytokines, amyloid hypothesis, pathogenesis, therapeutic target
MeSH terms
Alzheimer Disease, Animals, Humans, Inflammation

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