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Cited by 83Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurogenesis and neuroplasticity mechanisms

Proliferation in the Alzheimer Hippocampus Is due to Microglia, Not Astroglia, and Occurs at Sites of Amyloid Deposition

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Marlatt, Michael W., Bauer, Jan, Aronica, Eleonora, van Haastert, Elise S., Hoozemans, Jeroen J. M., Joels, Marian, Lucassen, Paul J.·2014·Neural Plasticity
DOI 10.1155/2014/693851PMC PMC4157009
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Abstract

Microglia and astrocytes contribute to Alzheimer’s disease (AD) etiology and may mediate early neuroinflammatory responses. Despite their possible role in disease progression and despite the fact that they can respond to amyloid deposition in model systems, little is known about whether astro- or microglia can undergo proliferation in AD and whether this is related to the clinical symptoms or to local neuropathological changes. Previously, proliferation was found to be increased in glia-rich regions of the presenile hippocampus. Since their phenotype was unknown, we here used two novel triple-immunohistochemical protocols to study proliferation in astro- or microglia in relation to amyloid pathology. We selected different age-matched cohorts to study whether proliferative changes relate to clinical severity or to neuropathological changes. Proliferating cells were found across the hippocampus but never in mature neurons or astrocytes. Almost all proliferating cells were colabeled with Iba1+, indicating that particularly microglia contribute to proliferation in AD. Proliferating Iba1+ cells was specifically seen within the borders of amyloid plaques, indicative of an active involvement in, or response to, plaque accumulation. Thus, consistent with animal studies, proliferation in the AD hippocampus is due to microglia, occurs in close proximity of plaque pathology, and may contribute to the neuroinflammation common in AD.

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  • DS-AD mice show increased accumulation of activated microglia associated with Aβ plaques, with increased phagocytic activity.

    “Our results demonstrate an increased accumulation of activated microglia associated with Aβ plaques in DS-AD mice, with increased phagocytic activity”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [95]

    The Discussion (page unavailable) reports activated microglia proliferating around Aβ plaques in an AD mouse model, which supports the general plaque-association point. It does not report findings in DS-AD mice or increased phagocytic activity; its own study examined human hippocampal tissue. (LLM, conf=0.88)

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References 93 · Cited by 83

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Authors
Marlatt, M. W., Bauer, J., Aronica, E., van Haastert, E. S., Hoozemans, J. J. M., Joels, M., & Lucassen, P. J.
Affiliations
  • University of Amsterdam (NL)
  • Medical University of Vienna (AT)
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Department of Pathology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • Swammerdam Institute for Life Sciences-Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands
Corresponding author
Lucassen, Paul J.
ORCID
Venue
Neural Plasticity
Publisher
Wiley
Published
2014
Volume
2014
Pages
1-12
ISSN
  • 1687-5443 (ISSN-L)
  • 2090-5904
DOI
10.1155/2014/693851
PMC
PMC4157009
OpenAlex
W2041572758
Cited by
83
References
93
Citations by year
2026: 2 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 8 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 8 · 2016: 8 · 2015: 6 · 2014: 4
FWCI
4.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Neural Plasticity (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • UvA-DARE (University of Amsterdam) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • European Union (MEST-CT-2005-020013)
  • Dutch Brain Foundation (MEST-CT-2005-020013)
  • International Parkinson’s Foundation (MEST-CT-2005-020013)
  • Alzheimer Nederland (MEST-CT-2005-020013)
  • Internationale Stichting Alzheimer Onderzoek (MEST-CT-2005-020013)
  • Stichting Epilepsie Instellingen Nederland (MEST-CT-2005-020013)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
Alzheimer's disease, microglia, astrocytes, glial cell proliferation, amyloid plaques, hippocampus, neuroinflammation, Iba1
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Astrocytes, Female, Hippocampus, Humans, Male, Neurons, Microglia, Cell Proliferation, Plaque, Amyloid

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