Recent advances in Alzheimer’s disease treatment MCQs With Answer

Recent advances in Alzheimer’s disease treatment MCQs With Answer

Introduction: This quiz-based review covers contemporary therapeutic strategies and clinical developments in Alzheimer’s disease relevant for M.Pharm students. It summarizes mechanisms, key clinical trials, biomarkers, and safety considerations of novel approaches — including anti-amyloid monoclonal antibodies, tau-targeting modalities, BACE inhibitors, antisense oligonucleotides, ApoE-directed strategies, microglial modulators, and neuroprotective or regenerative therapies. Emphasis is placed on translational pharmacology, trial endpoints and adverse events such as ARIA, to help students critically appraise recent literature and prepare for advanced coursework or research in neuropharmacology. Answers are provided to facilitate self-assessment and deeper study of each topic.

Q1. Which of the following best describes the primary mechanism of action of aducanumab?

• Blocks beta-secretase activity to reduce Aβ production
• Inhibits tau aggregation by stabilizing monomeric tau
• Binds aggregated Aβ fibrils/oligomers and promotes microglial-mediated clearance
• Acts as an NMDA receptor antagonist to reduce excitotoxicity

Correct Answer: Binds aggregated Aβ fibrils/oligomers and promotes microglial-mediated clearance

Q2. What is the most characteristic imaging-related adverse event associated with anti-amyloid monoclonal antibody therapy?

• Progressive multifocal leukoencephalopathy (PML)
• Amyloid-related imaging abnormalities (ARIA), including edema and microhemorrhage
• Posterior reversible encephalopathy syndrome (PRES)
• Cerebral atrophy acceleration visible on MRI

Correct Answer: Amyloid-related imaging abnormalities (ARIA), including edema and microhemorrhage

Q3. Aducanumab’s pivotal clinical programme included which pair of phase 3 trials?

• CLARITY-AD and TRAILBLAZER-ALZ
• EMERGE and ENGAGE
• SOLANEZUMAB-1 and SOLANEZUMAB-2
• ALZ-801 and ALZ-802

Correct Answer: EMERGE and ENGAGE

Q4. Lecanemab’s phase 3 registration trial is commonly known by what name?

• EMERGE
• ENGAGE
• CLARITY AD
• TRAILBLAZER-ALZ

Correct Answer: CLARITY AD

Q5. Which phase 3 trial program is associated with donanemab?

• CLARITY AD
• TRAILBLAZER-ALZ 2
• EXPEDITION
• APOLLO

Correct Answer: TRAILBLAZER-ALZ 2

Q6. Why were many BACE (beta-secretase) inhibitors discontinued in late-stage clinical trials?

• They caused excessive microglial activation and seizures
• They showed off-target Notch inhibition leading to severe immunosuppression
• Despite lowering Aβ production, several trials reported cognitive worsening and adverse effects
• They increased tau phosphorylation and accelerated tangles formation

Correct Answer: Despite lowering Aβ production, several trials reported cognitive worsening and adverse effects

Q7. Which plasma biomarker has shown the highest sensitivity and specificity for early Alzheimer’s disease prediction in recent studies?

• Plasma total tau (t-tau)
• Plasma phosphorylated tau at threonine 217 (p-tau217)
• Plasma amyloid-beta 42/40 ratio only
• Plasma neurofilament light chain (NfL) exclusively

Correct Answer: Plasma phosphorylated tau at threonine 217 (p-tau217)

Q8. How do antisense oligonucleotides (ASOs) targeting tau aim to modify disease biology?

• They degrade extracellular tau aggregates via Fc-mediated phagocytosis
• They reduce tau mRNA levels, lowering intracellular tau protein synthesis
• They enhance tau hyperphosphorylation to sequester toxic species
• They increase tau expression to stabilize microtubules

Correct Answer: They reduce tau mRNA levels, lowering intracellular tau protein synthesis

Q9. Therapeutic strategies directed at APOE4 aim to achieve which of the following pharmacological outcomes?

• Direct inhibition of cholinesterase activity
• Enhancement of ApoE4 lipidation or reduction of ApoE4-mediated amyloid aggregation and neuroinflammation
• Blockade of NMDA receptors to prevent excitotoxicity
• Activation of beta-secretase to clear amyloid peptides

Correct Answer: Enhancement of ApoE4 lipidation or reduction of ApoE4-mediated amyloid aggregation and neuroinflammation

Q10. ALZ-801 (oral) is best described as which of the following?

• A monoclonal antibody against tau tangles
• A BACE inhibitor that irreversibly blocks beta-secretase
• An oral prodrug of tramiprosate that inhibits Aβ oligomer formation
• An antisense oligonucleotide reducing ApoE expression

Correct Answer: An oral prodrug of tramiprosate that inhibits Aβ oligomer formation

Q11. Which immunotherapeutic strategy is intended to enhance microglial phagocytosis through TREM2?

• TREM2 agonist monoclonal antibodies (e.g., AL002)
• BACE inhibitors to reduce substrate for microglia
• NMDA antagonists to reduce microglial activation
• Small molecule tau aggregation promoters

Correct Answer: TREM2 agonist monoclonal antibodies (e.g., AL002)

Q12. Which patient characteristic is associated with an increased risk of ARIA when treated with anti-amyloid antibodies?

• APOE ε4 carrier status, particularly homozygosity
• Young age (<60 years)
• Concurrent acetylcholinesterase inhibitor therapy
• Low baseline amyloid PET signal

Correct Answer: APOE ε4 carrier status, particularly homozygosity

Q13. Which PET ligand is commonly used to image tau neurofibrillary tangles in clinical research?

• Florbetapir (Amyloid PET tracer)
• Flortaucipir (AV-1451), a tau PET tracer
• FDG-PET for glucose metabolism only
• SPECT-DaT for dopaminergic terminals

Correct Answer: Flortaucipir (AV-1451), a tau PET tracer

Q14. Why did gamma-secretase inhibitors cause safety concerns in Alzheimer’s drug development?

• They selectively increased Aβ42 production
• They inhibited Notch signaling leading to gastrointestinal and immunologic toxicity
• They caused uncontrollable microglial activation and seizures
• They directly phosphorylated tau and increased tangle formation

Correct Answer: They inhibited Notch signaling leading to gastrointestinal and immunologic toxicity

Q15. What is the principal difference between passive and active immunotherapy for Alzheimer’s disease?

• Passive immunotherapy uses small molecules; active uses monoclonal antibodies
• Passive immunotherapy administers exogenous antibodies; active immunotherapy elicits host antibody production via vaccination
• Passive immunotherapy targets tau only; active targets amyloid only
• Passive immunotherapy permanently modifies DNA; active does not

Correct Answer: Passive immunotherapy administers exogenous antibodies; active immunotherapy elicits host antibody production via vaccination

Q16. Which of the following remains an approved symptomatic therapy that modulates glutamatergic neurotransmission?

• Memantine, an NMDA receptor antagonist
• Verubecestat, a BACE inhibitor
• Lecanemab, an anti-amyloid monoclonal antibody
• BIIB080, an antisense oligonucleotide

Correct Answer: Memantine, an NMDA receptor antagonist

Q17. What is the rationale behind therapeutic plasma exchange with albumin replacement in Alzheimer’s research?

• To deliver monoclonal antibodies directly to the brain
• To remove circulating amyloid-beta bound to plasma proteins and shift peripheral-central equilibrium
• To replace deficient clotting factors implicated in dementia
• To boost CSF tau clearance by increasing intracranial pressure

Correct Answer: To remove circulating amyloid-beta bound to plasma proteins and shift peripheral-central equilibrium

Q18. Which clinical endpoint has been frequently used in recent anti-amyloid phase 3 trials to assess cognitive and functional change?

• MADRS (Montgomery–Åsberg Depression Rating Scale)
• CDR-SB (Clinical Dementia Rating – Sum of Boxes)
• UPDRS (Unified Parkinson’s Disease Rating Scale)
• HbA1c levels

Correct Answer: CDR-SB (Clinical Dementia Rating – Sum of Boxes)

Q19. Which rationale supports combining anti-amyloid and anti-tau therapies in future Alzheimer’s treatment strategies?

• Amyloid and tau are independent and non-interacting pathways, so combination is redundant
• Targeting both upstream amyloid pathology and downstream tau pathology may produce additive or synergistic disease-modifying effects
• Combination therapies only increase adverse events with no potential benefit
• Anti-amyloid therapies convert tau into a non-toxic isoform directly

Correct Answer: Targeting both upstream amyloid pathology and downstream tau pathology may produce additive or synergistic disease-modifying effects

Q20. Which statement best reflects the current status and main challenge of stem cell–based approaches in Alzheimer’s disease?

• Stem cell therapy is standard of care with reproducible cognitive restoration
• Stem cells can replace lost neurons and deliver trophic support, but integration, targeted differentiation and immune rejection remain major challenges
• Stem cell approaches primarily reduce amyloid plaques through enzymatic degradation
• There is no preclinical rationale for stem cells in neurodegenerative repair

Correct Answer: Stem cells can replace lost neurons and deliver trophic support, but integration, targeted differentiation and immune rejection remain major challenges

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