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Article
Open AccessCystatin F attenuates neuroinflammation and demyelination following murine coronavirus infection of the central nervous system
Cystatin F is a secreted lysosomal cysteine protease inhibitor that has been implicated in affecting the severity of demyelination and enhancing remyelination in pre-clinical models of immune-mediated demyelin...
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Article
Open AccessSelective targeting and modulation of plaque associated microglia via systemic hydroxyl dendrimer administration in an Alzheimer’s disease mouse model
In Alzheimer’s disease (AD), microglia surround extracellular plaques and mount a sustained inflammatory response, contributing to the pathogenesis of the disease. Identifying approaches to specifically target...
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Article
Microglia promote anti-tumour immunity and suppress breast cancer brain metastasis
Breast cancer brain metastasis (BCBM) is a lethal disease with no effective treatments. Prior work has shown that brain cancers and metastases are densely infiltrated with anti-inflammatory, protumourigenic tu...
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Article
Open AccessA Trem2R47H mouse model without cryptic splicing drives age- and disease-dependent tissue damage and synaptic loss in response to plaques
The TREM2 R47H variant is one of the strongest genetic risk factors for late-onset Alzheimer’s Disease (AD). Unfortunately, many current Trem2 R47H mouse models are associated with cryptic mRNA splicing of the mu...
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Article
Open AccessCortical diurnal rhythms remain intact with microglial depletion
Microglia are subject to change in tandem with the endogenously generated biological oscillations known as our circadian rhythm. Studies have shown microglia harbor an intrinsic molecular clock which regulates...
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Article
Open AccessMicroglia as hackers of the matrix: sculpting synapses and the extracellular space
Microglia shape the synaptic environment in health and disease, but synapses do not exist in a vacuum. Instead, pre- and postsynaptic terminals are surrounded by extracellular matrix (ECM), which together with...
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Article
Open AccessSystematic phenoty** and characterization of the 5xFAD mouse model of Alzheimer’s disease
Mouse models of human diseases are invaluable tools for studying pathogenic mechanisms and testing interventions and therapeutics. For disorders such as Alzheimer’s disease in which numerous models are being g...
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Article
Open AccessGeneration of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer’s disease-like pathology
The majority of Alzheimer’s disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial aut...
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Article
Open AccessEffects of long-term and brain-wide colonization of peripheral bone marrow-derived myeloid cells in the CNS
Microglia, the primary resident myeloid cells of the brain, play critical roles in immune defense by maintaining tissue homeostasis and responding to injury or disease. However, microglial activation and dysfu...
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Article
Open AccessSustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model
Many risk genes for the development of Alzheimer’s disease (AD) are exclusively or highly expressed in myeloid cells. Microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for their...
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Article
Open AccessPrevention of C5aR1 signaling delays microglial inflammatory polarization, favors clearance pathways and suppresses cognitive loss
Pharmacologic inhibition of C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, suppressed pathology and cognitive deficits in Alzheimer's disease (AD) mouse models. To validate that...
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Article
Necroptosis activation in Alzheimer's disease
The mechanisms underpinning neuronal death in Alzheimer's disease (AD) remain unclear. Caccamo and colleagues show that necroptosis contributes to neurodegeneration in AD. Blocking necroptosis reduced neuronal...
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Article
Open AccessElimination of microglia improves cognitive function following cranial irradiation
Cranial irradiation for the treatment of brain cancer elicits progressive and severe cognitive dysfunction that is associated with significant neuropathology. Radiation injury in the CNS has been linked to per...
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Article
Open AccessColony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice
Microglia are dependent upon colony-stimulating factor 1 receptor (CSF1R) signaling for their survival in the adult brain, with administration of the dual CSF1R/c-kit inhibitor PLX3397 leading to the near-comp...
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Article
Open AccessSpatial Frequency Domain Imaging of Intrinsic Optical Property Contrast in a Mouse Model of Alzheimer’s Disease
Extensive changes in neural tissue structure and function accompanying Alzheimer’s disease (AD) suggest that intrinsic signal optical imaging can provide new contrast mechanisms and insight for assessing AD ap...
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Chapter
Impact of A β and Tau on Cognition in Mouse Models of Alzheimer’s Disease
Since the first patient was diagnosed with Alzheimer’s disease, scientists have attempted to study the pathological features associated with the disease in an attempt to find a cure. Although several biologica...
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Article
Intracellular amyloid-β in Alzheimer's disease
This Review examines the current evidence supporting a role for intracellular amyloid-β (Aβ) in the pathogenesis of Alzheimer's disease. Intracellular Aβ accum...
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Chapter and Conference Paper
Amyloid Peptide-Mediated Hypoxic Regulation of Ca2+ Channels in PC12 Cells
The incidence of dementias such as Alzheimer’s Disease (AD) is dramatically increased in patients who have previously suffered prolonged hypoxic or ischemic episodes. Such episodes commonly arise as a conseque...
