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Updated: May 16, 2026
Quantitative 3D In Silico Modeling (q3DISM) of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
Mrp14 deficiency ameliorates amyloid β burden by increasing microglial phagocytosis and modulation of amyloid
Markus P Kummer1, Thomas Vogl, Daisy Axt
1Clinical Neurosciences Unit, Department of Neurology, University of Bonn, 53105 Bonn, Germany.
Abstract:
Neuroinflammation plays a fundamental role in the pathogenesis of Alzheimer's disease (AD), resulting in the extensive activation of microglial and astroglial cells. Here we describe the role of myeloid-related protein Mrp14, a recently described amplifier of inflammation, in Alzheimer's disease and in the related amyloid precursor protein/presenilin1 (APP/PS1) mouse model. Detection of Mrp14 in control, mildly cognitive impaired, and AD patients revealed a strong induction of Mrp14 in protein extracts as well as in the cerebrospinal fluid, but not in blood plasma. In APP/PS1 mice, Mrp14 and its heterodimeric partner Mrp8 was found to be upregulated in microglial cells surrounding amyloid plaques. Functionally, loss of Mrp14 led to increased phagocytosis of fibrillar amyloid β (Aβ) in microglia cells in vitro and in vivo. Generating APP/PS1-transgenic mice deficient for Mrp14, we observed a decrease of key cytokines involved in APP processing, a reduction of BACE1 expression and activity, and consequently overall Aβ deposition. We therefore conclude that Mrp14 promotes APP processing and Aβ accumulation under neuroinflammatory conditions.
Insights
Myeloid-related protein Mrp14 amplifies inflammation in Alzheimer's disease (AD). Loss of Mrp14 reduces amyloid-beta deposition by enhancing microglial phagocytosis and decreasing BACE1 activity.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Neuroinflammation is central to Alzheimer's disease (AD) pathogenesis.
- Microglial and astroglial cells are extensively activated in AD.
- Myeloid-related protein Mrp14 is a known amplifier of inflammation.
Purpose of the Study:
- To investigate the role of Mrp14 in Alzheimer's disease.
- To examine Mrp14 expression in AD patients and a mouse model.
- To determine the functional impact of Mrp14 deficiency on amyloid pathology.
Main Methods:
- Detected Mrp14 in human cerebrospinal fluid and protein extracts from AD patients.
- Analyzed Mrp14 and Mrp8 expression in microglial cells of APP/PS1 mice.
- Assessed phagocytosis of amyloid-beta by microglia.
- Generated and analyzed APP/PS1 mice deficient for Mrp14.
Main Results:
- Mrp14 was significantly upregulated in AD patients' cerebrospinal fluid and brain tissue.
- Mrp14 and Mrp8 were elevated in microglia surrounding amyloid plaques in APP/PS1 mice.
- Loss of Mrp14 enhanced microglial phagocytosis of amyloid-beta.
- APP/PS1 mice lacking Mrp14 showed reduced BACE1 activity and amyloid deposition.
Conclusions:
- Mrp14 promotes amyloid precursor protein processing and amyloid-beta accumulation in neuroinflammation.
- Targeting Mrp14 may offer a therapeutic strategy for Alzheimer's disease.
