Distinct and non-redundant roles of microglia and myeloid subsets in mouse models of Alzheimer's disease

Alexander Mildner, Bernhard Schlevogt, Katrin Kierdorf, Chotima Böttcher, Daniel Erny, Markus P Kummer, Michael Quinn, Wolfgang Brück, Ingo Bechmann, Michael T Heneka, Josef Priller, Marco Prinz

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Mononuclear phagocytes are important modulators of Alzheimer's disease (AD), but the specific functions of resident microglia, bone marrow-derived mononuclear cells, and perivascular macrophages have not been resolved. To elucidate the spatiotemporal roles of mononuclear phagocytes during disease, we targeted myeloid cell subsets from different compartments and examined disease pathogenesis in three different mouse models of AD (APP(swe/PS1), APP(swe), and APP23 mice). We identified chemokine receptor 2 (CCR2)-expressing myeloid cells as the population that was preferentially recruited to β-amyloid (Aβ) deposits. Unexpectedly, AD brains with dysfunctional microglia and devoid of parenchymal bone marrow-derived phagocytes did not show overt changes in plaque pathology and Aβ load. In contrast, restriction of CCR2 deficiency to perivascular myeloid cells drastically impaired β-amyloid clearance and amplified vascular Aβ deposition, while parenchymal plaque deposition remained unaffected. Together, our data advocate selective functions of CCR2-expressing myeloid subsets, which could be targeted specifically to modify disease burden in AD.

Original languageEnglish
Pages (from-to)11159-71
Number of pages13
JournalJournal of Neuroscience
Volume31
Issue number31
DOIs
Publication statusE-pub ahead of print - 3 Aug 2011

Keywords / Materials (for Non-textual outputs)

  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Animals
  • Bone Marrow Transplantation
  • CD11b Antigen
  • Cell Death
  • Cell Proliferation
  • Central Nervous System
  • Disease Models, Animal
  • Gene Expression Regulation
  • Green Fluorescent Proteins
  • Ki-67 Antigen
  • Mice
  • Mice, Transgenic
  • Microdissection
  • Microglia
  • Mutation
  • Myeloid Cells
  • Receptors, CCR2
  • Whole-Body Irradiation
  • Journal Article
  • Research Support, Non-U.S. Gov't

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