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Questions and Answers
What type of neurons are primarily lost in Alzheimer's disease, contributing to cognitive decline?
Which region of the brain is notably affected in terms of shrinkage in Alzheimer's disease?
What are the two key hallmarks of Alzheimer's disease?
Which type of memory is primarily affected early in the course of Alzheimer's disease?
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What is the role of the entorhinal cortex and hippocampus in memory?
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Which type of memory allows recall for several seconds to a minute without rehearsal?
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In the context of Alzheimer's disease, what specifically does neurofibrillary tangles consist of?
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As Alzheimer's disease progresses, which type of memory becomes impaired alongside episodic and semantic memory?
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What is the first brain structure affected by Alzheimer's disease?
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How long before symptoms do changes from Alzheimer's disease typically begin?
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What effect does chronic alcohol use have on adult neurogenesis?
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Which factor is associated with elevated levels of phosphorylated eIF2α in sporadic Alzheimer's disease brains?
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Which of the following conditions can induce apoptotic damage affecting adult neurogenesis?
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Which cognitive function is primarily affected as Alzheimer's disease progresses?
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What is a characteristic of adult hippocampal neurogenesis?
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What is a potential consequence of dysregulated translation in the context of neurodegeneration?
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What is the primary role of mesenchymal stem/stromal cells (MSCs) in neurological diseases?
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How does the loss of TREM2 function impact neurodegenerative conditions?
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What is a significant genetic risk factor associated with late-onset Alzheimer's Disease?
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Which of the following memory types is NOT categorized under long-term memory?
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How can the efficacy of MSC therapy be improved prior to transplantation?
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What aspect of memory is primarily affected early in the course of Alzheimer's Disease?
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What cellular treatment approach has been shown to restore TREM2 function in Alzheimer's models?
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Which type of memory involves the conscious recall of facts and general knowledge?
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Study Notes
Alzheimer’s Disease
- Alzheimer’s disease (AD) is a neurodegenerative disorder that causes memory loss and other cognitive impairments.
- It is the most common cause of dementia.
Neuropathology of Alzheimer’s Disease
- The brain of an AD patient exhibits significant shrinkage of the neocortex, enlarged ventricles, and a smaller hippocampus.
- This atrophy is due to the loss of neurons, including pyramidal, cholinergic, noradrenergic, and serotonergic neurons.
Hallmarks of Alzheimer’s Disease
- Two key hallmarks of AD are:
- Amyloid plaques: These are formed by the accumulation of amyloid-beta protein in the brain.
- Neurofibrillary tangles: They are made up of tau protein, which is abnormally phosphorylated.
Normal Memory Processing
- Short-term memory (STM): It allows recall for brief periods (seconds to a minute) without rehearsal.
- Long-term memory (LTM): Stores large quantities of information for prolonged durations, potentially a lifetime.
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Explicit (conscious) memory:
- Semantic memory: Holds facts and general knowledge.
- Episodic memory: Stores personally experienced events.
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Implicit (unconscious) memory:
- Classical conditioning: A type of learning where an association is made between a neutral stimulus and a response.
- Priming memory: Enhanced identification of objects or words due to prior exposure.
- Procedural memory: Knowledge of cognitive and motor skills.
Progression of Alzheimer’s Disease
- AD progresses over time, eventually leading to severe cognitive decline and dependence on caregivers.
- The disease starts about 15 years before symptoms appear in a prodromal form called amnesic mild cognitive impairment.
- The entorhinal cortex is impacted first, causing impairments in episodic memory.
- As the disease spreads to other areas of the neocortex, other cognitive functions are affected, and eventually dementia becomes evident.
Adult Neurogenesis
- The process of adult neurogenesis in the hippocampus is disrupted in several neuropsychiatric conditions, including major depression, schizophrenia, and chronic drug/alcohol abuse.
- Psychosocial stress can negatively impact neurogenesis, leading to a decrease in the number of stem cells, progenitors, and mature neurons in the hippocampus.
Mesenchymal Stem Cell Therapy
- Mesenchymal stem/stromal cells (MSCs) have shown potential for treating neurological diseases.
- MSCs can be isolated from different tissues, including bone marrow, umbilical cord, and adipose tissue.
- MSCs exert neuroprotective effects by releasing cytokines, trophic factors, and microRNAs, which can be released directly or packaged in micro vesicles and exosomes.
Cell therapy to Restore Microglial Function in Alzheimer's
- TREM2-R47H is a genetic risk factor for AD.
- Loss of function of TREM2 results in Nasu-Hakola disease, leading to early-onset neurodegeneration.
- Replacing mutant microglia with circulation-derived myeloid cells (CDMCs) through hematopoietic cell transplantation can restore TREM2 function in a mouse model of AD.
Clinical Trials for Amyotrophic Lateral Sclerosis
- Clinical trials using mesenchymal stem/stromal cells have been conducted for Amyotrophic Lateral Sclerosis (ALS).
- Measures such as the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) are used to evaluate the effectiveness of treatment interventions.
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Description
Explore the complexities of Alzheimer’s disease, a prevalent neurodegenerative disorder characterized by memory loss and cognitive decline. Learn about its neuropathology, including the impacts on brain structure and the critical hallmarks such as amyloid plaques and neurofibrillary tangles.
