Related Experiment Video
Updated: Dec 23, 2025
Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
The Amyloid-beta rich CNS environment alters myeloid cell functionality independent of their origin
Natalia Drost1, Judith Houtman1,2, Zoltán Cseresnyés3,4
1Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117, Berlin, Germany.
Abstract:
Microglia, the innate immune cells of the central nervous system (CNS) survey their surroundings with their cytoplasmic processes, phagocytose debris and rapidly respond to injury. These functions are affected by the presence of beta-Amyloid (Aβ) deposits, hallmark lesions of Alzheimer's disease (AD). We recently demonstrated that exchanging functionally altered endogenous microglia with peripheral myeloid cells did not change Aβ-burden in a mouse model mimicking aspects of AD at baseline, and only mildly reduced Aβ plaques upon stimulation. To better characterize these different myeloid cell populations, we used long-term in vivo 2-photon microscopy to compare morphology and basic functional parameters of brain populating peripherally-derived myeloid cells and endogenous microglia. While peripherally-derived myeloid cells exhibited increased process movement in the non-diseased brain, the Aβ rich environment in an AD-like mouse model, which induced an alteration of surveillance functions in endogenous microglia, also restricted functional characteristics and response to CNS injury of newly recruited peripherally-derived myeloid cells. Our data demonstrate that the Aβ rich brain environment alters the functional characteristics of endogenous microglia as well as newly recruited peripheral myeloid cells, which has implications for the role of myeloid cells in disease and the utilization of these cells in Alzheimer's disease therapy.
Insights
Alzheimer's disease (AD) brain environments impair both resident microglia and infiltrating myeloid cells. This suggests the brain's amyloid-beta rich milieu alters myeloid cell function, impacting AD therapies.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are central nervous system (CNS) immune cells surveilling and responding to injury.
- Beta-amyloid (Aβ) deposits in Alzheimer's disease (AD) alter microglial functions.
- Peripheral myeloid cells were previously shown to have limited impact on Aβ burden in AD models.
Purpose of the Study:
- To compare the morphology and function of endogenous microglia and peripheral myeloid cells in vivo.
- To investigate how the AD brain environment affects these myeloid populations.
- To understand the implications for myeloid cell-based Alzheimer's disease therapies.
Main Methods:
- Long-term in vivo 2-photon microscopy was used.
- Morphology and basic functional parameters of myeloid cells were compared.
- Studies were conducted in both non-diseased and AD-like mouse models.
Main Results:
- Peripherally-derived myeloid cells showed increased process movement in healthy brains.
- In an AD-like model, the Aβ-rich environment restricted the function of both endogenous microglia and peripheral myeloid cells.
- Both cell types showed altered surveillance and response to CNS injury in the diseased brain.
Conclusions:
- The amyloid-beta rich environment in the AD brain significantly alters the functional characteristics of both endogenous microglia and infiltrating peripheral myeloid cells.
- These findings have critical implications for understanding myeloid cell roles in AD pathogenesis.
- The study highlights challenges for utilizing peripheral myeloid cells as a therapeutic strategy for Alzheimer's disease.
