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Cited by 64Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Microglial motility in Alzheimer’s disease and after Aβ42 immunotherapy: a human post-mortem study

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Franco-Bocanegra, Diana K., George, Bethany, Lau, Laurie C., Holmes, Clive, Nicoll, James A. R., Boche, Delphine·2019·Acta Neuropathologica Communications
DOI 10.1186/s40478-019-0828-xPMC PMC6842157
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Abstract

Microglial function is highly dependent on cell motility, with baseline motility required for homeostatic surveillance activity and directed motility to migrate towards a source of injury. Experimental evidence suggests impaired microglial motility in Alzheimer’s disease (AD) and therefore we have investigated whether the expression of proteins associated with motility is altered in AD and affected by the Aβ immunotherapy using post-mortem brain tissue of 32 controls, 44 AD cases, and 16 AD cases from our unique group of patients immunised against Aβ42 (iAD). Sections of brain were immunolabelled and quantified for (i) the motility-related microglial proteins Iba1, cofilin 1 (CFL1), coronin-1a (CORO1A) and P2RY12, and (ii) pan-Aβ, Aβ42 and phosphorylated tau (ptau). The neuroinflammatory environment was characterised using Meso Scale Discovery multiplex assays. The expression of all four motility-related proteins was unmodified in AD compared with controls, whereas Iba1 and P2RY12, the homeostatic markers, were increased in the iAD group compared with AD. Iba1 and P2RY12 showed significant positive correlations with Aβ in controls but not in the AD or iAD groups. Pro- and anti-inflammatory proteins were increased in AD, whereas immunotherapy appears to result in a slightly less pro-inflammatory environment. Our findings suggest that as Aβ appears during the ageing process, the homeostatic Iba1 and P2RY12 –positive microglia respond to Aβ, but this response is absent in AD. Aβ-immunisation promoted increased Iba1 and P2RY12 expression, likely reflecting increased baseline microglial motility but without restoring the profile observed in controls.

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  • The ACTR2 (encoding ARP2) and CFL1 (Cofilin 1) genes play significant roles in actin remodeling, enabling both baseline movement (ruffling or branching) and chemotactic motility (migration).

    “The ACTR2 (encoding ARP2) and CFL1 (Cofilin 1) genes play significant roles in actin remodeling, enabling both baseline movement (ruffling or branching) and chemotactic motility (migration) [18, 28, 29].”

    From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [28]

    The Introduction describes CFL1 as an actin-binding protein, links Arp2/3 to actin branching, and says actin reorganisation is essential to both baseline and directed microglial motility. It does not identify ACTR2 as the gene encoding ARP2 or establish a specific role for ACTR2 in those forms of movement; the Discussion says the Arp2/3 complex was not evaluated in this study. Page numbers are unavailable in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • ARP2, CAP1, and CFL1 are proteins related to engulfment processes through actin-based motility mechanisms, and were recently associated with AD resilience according to protein coexpression analysis.

    “In this context, ARP2, CAP1, and CFL1 are proteins related to engulfment processes through actin-based motility mechanisms [28, 29], that were recently associated with AD resilience according to protein coexpression analysis [39].”

    From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [28]

    The Introduction (page not provided) describes Arp2/3 and CFL1 as involved in actin organization and links actin-based microglial structures to migration and phagocytosis. It does not identify CAP1 or establish its role in engulfment. The AD-resilience finding is attributed to a different citation, [39], so it is not judged against this source. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • There is no clear evidence of CFL1 and CAP1 changes in AD.

    “Although there is no clear evidence of CFL1 and CAP1 changes in AD [28, 72],”

    From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [28]

    The Results section (Microglial motility-related proteins; page not provided) reports no significant difference in CFL1 between AD cases and controls. The four proteins examined were Iba1, CFL1, P2RY12 and CORO1A, not CAP1, so this paper does not support the CAP1 part of the claim. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 42

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Authors
Franco-Bocanegra, D. K., George, B., Lau, L. C., Holmes, C., Nicoll, J. A. R., & Boche, D.
Affiliations
  • Southampton General Hospital (GB)
  • University of Southampton (GB)
Corresponding author
Boche, Delphine
ORCID
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2019-11-08
Volume
7
Issue
1
Pages
174-174
ISSN
2051-5960 (ISSN-L)
DOI
10.1186/s40478-019-0828-x
PMC
PMC6842157
OpenAlex
W2987376294
Cited by
64
References
60
Citations by year
2026: 3 · 2025: 5 · 2024: 15 · 2023: 7 · 2022: 12 · 2021: 12 · 2020: 9 · 2018: 1
FWCI
3.63
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Conacyt scholarship (270152 / 438262)
  • Alzheimer’s Research UK (ART/PG2006/4)
  • Alzheimer's Research UK (ART-EXT2010-1, ARUK-EG2015A-4)
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
microglial motility, Alzheimer's disease, Iba1, P2Y12 receptor, cofilin-1, CORO1A, neuroinflammation, phosphorylated tau, postmortem brain
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Brain, Cell Movement, Female, Humans, Immunotherapy, Male, Peptide Fragments, Amyloid beta-Peptides, Microglia

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