Questions and Answers
What was realized by Alois Alzheimer in the context of dementia?
In which mouse model are astrocytes observed to undergo complex morphological changes?
What is expressed by a decrease in the GFAP-positive astroglial profiles?
At which stage do astrocytes in hippocampus, prefrontal and entorhinal cortices demonstrate signs of atrophy and astrodegeneration?
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In which region were the earliest signs of atrophy observed?
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What is a characteristic of astrodegeneration in astrocytes?
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At which age do astrocytes in the hippocampus demonstrate signs of atrophy and astrodegeneration?
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What is the pattern of atrophic changes in astrocytes?
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What is the primary function of the vesicular trafficking system in astrocytes?
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What is the effect of an increase in [Ca2+]i on glutamatergic vesicle motility?
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What is a characteristic feature of the aging CNS?
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What is the characteristic of peptidergic vesicles in terms of their response to an increase in [Ca2+]i?
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At what age does the myelination of the CNS profile peak?
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What is the role of oligodendrocytes in the human brain?
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What is associated with the decrease in the self-renewal capacity of oligodendroglial precursors/NG2 cells?
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What is observed in the astrocytes of 3xTg-AD mice in the pre-symptomatic phase of Alzheimer's disease?
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What can induce cytosolic Ca2+ overload in oligodendrocytes?
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What is the consequence of oligodendrocyte degeneration and death in the brain?
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What is the effect of an increase in [Ca2+]i on recycling peptidergic vesicles?
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What is a possible contributor to oligodendroglia death in the context of AD?
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What is the regulatory mechanism that maintains vesicle traffic in astrocytes?
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What is a consequence of oligodendrocyte death and myelin destruction in AD?
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What type of receptors do oligodendrocytes express that are permeable to Ca2+?
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What is a possible cause of abnormal Ca2+ homeostasis and signalling in oligodendrocytes?
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What is the possible reason for oligodendrocytes being damaged when exposed to β-amyloid?
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What is the effect of injecting β-amyloid into white matter on oligodendrocytes?
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What is the role of mutant PS1 in the demyelinating agent cuprizone experiment?
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What is a possible early marker of Alzheimer's disease?
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What is observed in the later phase of 3xTg-AD mice?
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What is the role of microglial cells in Alzheimer's disease?
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What is observed in human AD post-mortem tissue?
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What is the possible consequence of alterations in myelin, oligodendroglia, and oligodendroglial precursors/NG2 cells?
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What is a possible consequence of the loss of microglial phagocytotic function in APP/PS1 mice?
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What triggers the activation of microglia in the AD context?
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What is necessary for the activation of microglia in response to β-amyloid injection?
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What is observed in the hippocampus of 3xTg-AD mice at 9 months of age?
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What is the effect of a spontaneous loss-of-function mutation in the TLR4 gene on microglial activation induced by Aβ?
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At which stage of AD do microglia become activated and recruited to Aβ plaques?
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What is observed in the progression of AD in 3xTg-AD mice?
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What is upregulated in AD animal models and in post-mortem AD brains?
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Study Notes
Astrocytes in Alzheimer's Disease
- Alois Alzheimer observed activated glial cells in close contact with pathologically altered neurons and described glia as a cellular component of the senile plaque.
- Astrocytes undergo complex morphological changes in animal AD models, including atrophy and astrodegeneration.
- In the triple transgenic 3xTg-AD mouse, astrocytes in hippocampus, prefrontal and entorhinal cortices demonstrate signs of atrophy and astrodegeneration at the early pre-symptomatic stages.
- These changes are expressed by a decrease in the GFAP-positive astroglial profiles, decreased somata volume, and a decrease in the number and branching of cell processes.
- The atrophic changes in astrocytes developed in a particular spatiotemporal pattern, with the earliest signs of atrophy observed in the entorhinal cortex, followed by the prefrontal cortex and hippocampus.
Vesicular Trafficking and Secretion in Astrocytes Are Altered in AD
- Vesicular trafficking and secretion in astrocytes are altered in AD, with glutamatergic vesicle motility accelerated by an increase in [Ca2+]i.
- Peptidergic vesicles and endolysosomes are slowed down by the same increase in [Ca2+]i.
- Astrocytes from 3xTg-AD mice isolated in the pre-symptomatic phase of the disease exhibit alterations in vesicle traffic, with diminished spontaneous mobility of peptidergic and endolysosomal vesicles.
Oligodendroglia in Disease
- Oligodendrocytes provide central myelination in the human brain, which degenerates and dies in various diseases, including AD.
- Myelin and oligodendrocyte defects in AD occur before the onset of symptoms and may be considered early markers.
- The loss of myelin is a characteristic feature of the aging CNS, particularly in the cerebral cortex, where decreased myelination and oligodendroglial demise have been identified.
Oligodendroglia in Alzheimer’s Disease
- Oligodendroglial cell death and myelin shortages are associated with abnormal Ca2+ homeostasis and signaling.
- Prolonged or excessive activation of ionotropic receptors, including l-glutamate and P2X receptors, induces cytosolic Ca2+ overload, leading to oligodendrocyte death and myelin destruction.
- Exposure to β-amyloid damages oligodendrocytes, and mutant PS1 increases their sensitivity to l-glutamate toxicity.
Microglia in Alzheimer’s Disease
- Microglial changes, both reactive and degenerative, are an important part of AD progression.
- Activated microglial cells secrete proinflammatory factors that may contribute to neuronal damage, and loss of microglial function has also been observed.
- In APP/PS1 mice, appearance of senile plaques coincided with the loss of microglial phagocytotic function, which reduced β-amyloid clearance and facilitated plaque formation.
- Degeneration of microglia can define neural tissue vulnerability to AD pathology.
- Activation of microglia in AD may also involve purinergic signaling, TLR4 and TLR2 Toll receptors, and P2X7 receptors.
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Description
Learn about the role of astrocytes in Alzheimer's disease, their pathological potential and reactivity in close contact with affected neurons.