Alzheimer’s Disease Therapeutic Strategies
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Alzheimer’s Disease Therapeutic Strategies

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Questions and Answers

Which therapeutic strategy is primarily associated with the acetylcholine pathway in the treatment of Alzheimer’s disease?

  • Anti-Ab monoclonal antibodies
  • Memantine
  • Nasal Insulin
  • Donepezil (Aricept) (correct)

    • What is the role of memantine in the context of Alzheimer’s disease?

  • It stimulates insulin production.
  • It is an antagonist at NMDA receptors. (correct)
  • It acts as a GLP-1 agonist.
  • It targets glucose metabolism.

    • Which factor is NOT typically associated with the development of Alzheimer’s disease?

  • Chronic hypertension (correct)
  • Inflammation in the brain
  • Altered proteolytic processing of APP
  • Impaired glucose metabolism

    • How does the hypothesis of Alzheimer's disease being related to insulin function describe the condition?

    <p>Alzheimer's is referred to as diabetes type III.</p> Signup and view all the answers

    Which of the following risk factors is associated with the development of Alzheimer's disease?

    <p>ApoE4 genotype</p> Signup and view all the answers

    What does the altered proteolytic processing of APP lead to in Alzheimer's disease?

    <p>Aggregation of Ab</p> Signup and view all the answers

    Which hypothesis relates to amyloid beta (Ab) in Alzheimer's disease?

    <p>Ab cascade hypothesis</p> Signup and view all the answers

    What is referred to as 'Alzheimer’s as diabetes type III'?

    <p>Impaired insulin signaling in cognitive functions</p> Signup and view all the answers

    Which risk factor is specifically identified in relation to Alzheimer's disease?

    <p>APOE4</p> Signup and view all the answers

    Which therapeutic strategy involves the use of glutamatergic regulators?

    <p>Cholinergic enhancers</p> Signup and view all the answers

    What is the primary effect of memantine in patients with moderate to severe Alzheimer’s disease?

    <p>It improves outcomes on various cognitive measures.</p> Signup and view all the answers

    Which medication is mentioned as a cholinergic enhancer when treating Alzheimer’s disease?

    <p>Donepezil</p> Signup and view all the answers

    What role does Type II Diabetes (T2DM) play in Alzheimer's disease according to the content?

    <p>It is identified as a risk factor for Alzheimer's disease.</p> Signup and view all the answers

    Which of the following is a consequence of impaired insulin signaling in Alzheimer’s disease patients?

    <p>Exacerbation of pathological features.</p> Signup and view all the answers

    What is the mechanism of action of GLP-1 receptor agonists like liraglutide in Alzheimer’s disease models?

    <p>They promote neuroprotection.</p> Signup and view all the answers

    Which outcome was NOT improved by memantine treatment in combination with donepezil?

    <p>Physical strength</p> Signup and view all the answers

    In addition to memantine, which treatment is suggested for the management of Alzheimer’s disease due to its role in insulin signaling?

    <p>GLP-1 receptor agonists</p> Signup and view all the answers

    What is one of the characteristics of the memantine treatment results described?

    <p>It was significantly better than placebo.</p> Signup and view all the answers

    What percentage did Lecanemab reportedly slow cognitive decline?

    <p>27%</p> Signup and view all the answers

    Who are recommended to receive Lecanemab treatment?

    <p>Patients with Mild Cognitive Impairment or mild Alzheimer’s disease</p> Signup and view all the answers

    Which of the following monoclonal antibodies has shown the greatest reported slowing of cognitive decline?

    <p>Donanemab</p> Signup and view all the answers

    What concern was raised regarding the Lecanemab clinical trial participants?

    <p>They were not representative of the Medicare population</p> Signup and view all the answers

    What action has the Centers for Medicare & Medicaid Services (CMS) taken regarding amyloid PET scans?

    <p>Expanded coverage to ensure better accessibility</p> Signup and view all the answers

    What is a key aspect of future strategies for Alzheimer's treatment mentioned in the content?

    <p>Developing a diverse generation of drugs to combine with amyloid-targeting drugs</p> Signup and view all the answers

    Which demographic groups were noted as underrepresented in the Lecanemab trial?

    <p>Black participants and women</p> Signup and view all the answers

    Which of the following is NOT a characteristic of Lecanemab mentioned?

    <p>It is recommended for severe Alzheimer's patients</p> Signup and view all the answers

    What is the primary consequence of sustained activation of the NMDA receptor?

    <p>Excitotoxicity and neuronal dysfunction</p> Signup and view all the answers

    What co-agonist is required for NMDA receptor activation?

    <p>Glycine</p> Signup and view all the answers

    Which of the following ions predominantly flows through the NMDA receptor upon activation?

    <p>Na+ and Ca2+</p> Signup and view all the answers

    What triggers the activation of the p38 MAPK pathway associated with apoptosis?

    <p>Excessive glutamate release</p> Signup and view all the answers

    What effect does S-nitrosylation have on the NMDA receptor?

    <p>Decreases channel activity</p> Signup and view all the answers

    Which of the following describes apoptotic-like excitotoxicity?

    <p>Cell death due to excessive glutamate release</p> Signup and view all the answers

    What is the role of the Mg2+ site in the NMDA receptor?

    <p>Maintains voltage-dependent blockade</p> Signup and view all the answers

    What process is triggered by Ca2+ influx through the NMDA receptor?

    <p>Activation of the nNOS pathway</p> Signup and view all the answers

    Study Notes

    Alzheimer’s Disease Therapeutic Strategies

    • Therapeutic strategies in Alzheimer's disease require recognition of the many factors influencing its development and risk factors.
    • Altered proteolytic processing of the amyloid precursor protein (APP) resulting in the production and aggregation of Ab is a key factor.
    • The Ab cascade hypothesis and UPR are pathways associated with Alzheimer's disease development.
    • Insulin in the brain: Alzheimer’s as diabetes type III indicates the potential link between diabetes and Alzheimer's disease.
    • Impaired glucose metabolism in Alzheimer's disease is a common characteristic.
    • Ab and oxidative stress are linked factors in Alzheimer's disease pathology.
    • Perturbed calcium homeostasis and excitotoxicity are critical mechanisms contributing to the disease.
    • Inflammation in Alzheimer's disease contributes to its progression.
    • Risk factors include ApoE4 genotype and maternal transmission.

    Anti-Ab Monoclonal Antibodies

    • LECANEMAB (Esai’s and Biogen’s) is an FDA-approved anti-Ab monoclonal antibody that slows cognitive and functional decline by 27%.
    • LECANEMAB is recommended for patients with Mild Cognitive Impairment (MCI) and mild Alzheimer’s disease, particularly those who are ApoE4 positive, but not for moderate or severe cases.
    • ADUCANUMAB (ADUHELM) (Biogen) is another anti-Ab monoclonal antibody with potential slowing of cognitive decline, but the effectiveness is disputed.
    • DONANEMAB (Lily) is another anti-Ab monoclonal antibody, potentially slowing cognitive decline by 35%.

    Glutamatergic Inhibitors

    • The glutamate pathway focuses on the role of sustained NMDA receptor activation leading to excessive Ca2+ influx (excitotoxicity), neuronal dysfunction, and cell death.
    • Memantine hydrochloride (Namenda, Namzaric) is a low-affinity NDMA receptor antagonist used to treat moderate to severe Alzheimer's disease.
    • NMDA receptors are composed of different subunits, NR1 and NR2A-D, responsible for binding sites for glycine (co-agonist) and glutamate (agonist).
    • NMDA receptor opening occurs when glutamate and glycine bind, and the Mg2+ block is removed, allowing Ca2+ and Na+ influx.
    • S-nitrosylation of cysteine protein in the receptor can reduce channel activity and is associated with the stimulation of the NMDA receptor.
    • Excessive release of glutamate or overstimulation of the NMDA receptor can lead to excitotoxic cell death.
    • Ca2+ influx following NMDA receptor activation triggers various processes that can lead to apoptosis, including activation of the p38 MAPK pathway and nNOS, resulting in NO formation and toxic effects.

    Cholinergic Enhancers

    • Donepezil (Aricept) is a cholinesterase inhibitor that increases acetylcholine levels in the brain.

    GLP-1 Agonists

    • GLP-1 receptor agonists (liraglutide) have been found to be neuroprotective in mouse models of Alzheimer's disease.
    • Insulin signaling is impaired in Alzheimer's disease patients, making it a potential target for treatment.

    Nasal Insulin

    • Nasal insulin administration is a potential treatment strategy for Alzheimer's disease, with clinical trials underway to assess its effectiveness.

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    Related Documents

    Alzheimer's Disease Therapies PDF

    Description

    Explore the therapeutic strategies for Alzheimer's disease, focusing on the underlying mechanisms and risk factors. This quiz covers altered proteolytic processing, the Amyloid cascade hypothesis, and the implications of brain insulin and glucose metabolism in the disease. Learn about the pivotal roles of oxidative stress, inflammation, and genetic factors like ApoE4 in Alzheimer's progression.

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