Screening methods for neurodegenerative disease drugs (Parkinson’s, Alzheimer’s) MCQs With Answer

Screening methods for neurodegenerative disease drugs (Parkinson’s, Alzheimer’s) MCQs With Answer

This quiz set is designed specifically for M.Pharm students studying Pharmacological and Toxicological Screening Methods-I. It focuses on in vitro, cell-based, and in vivo screening assays used to discover and characterize candidate therapeutics for Alzheimer’s and Parkinson’s diseases. Questions cover biochemical assays (amyloid aggregation, tau phosphorylation, acetylcholinesterase inhibition), cellular models, transgenic and toxin-induced animal models, behavioral and imaging endpoints, biomarkers, blood–brain barrier considerations, and high-throughput screening technologies. Emphasis is placed on choosing appropriate models and endpoints for efficacy, selectivity, toxicity, and translational relevance to clinical pathology.

Q1. Which in vitro assay is most commonly used to measure amyloid-beta fibril formation during high-throughput screening of anti-Alzheimer agents?

• Thioflavin T fluorescence assay
• MTT cell viability assay
• Seahorse mitochondrial respiration assay
• Rotarod motor coordination assay

Correct Answer: Thioflavin T fluorescence assay

Q2. Which transgenic mouse model overexpresses mutant human APP and PSEN1 leading to early amyloid plaque deposition and is widely used for anti-amyloid drug screening?

• 3xTg-AD (APP, PSEN1, tau)
• TauP301L model
• APP/PS1 double transgenic model
• A53T α-synuclein model

Correct Answer: APP/PS1 double transgenic model

Q3. For initial screening of compounds aimed at symptomatic treatment in Parkinson’s disease (improving motor deficits), which toxin-induced model is most commonly used in mice?

• MPTP-induced dopaminergic neuron loss
• Rotenone lung toxicity model
• 6-OHDA systemic administration in mice
• Transgenic LRRK2 overexpression in rats

Correct Answer: MPTP-induced dopaminergic neuron loss

Q4. Which biochemical assay directly measures acetylcholinesterase inhibitory activity of candidate drugs for Alzheimer’s symptomatic therapy?

• Ellman’s colorimetric assay
• Thioflavin S binding assay
• Western blot for phosphorylated tau
• Golgi staining for dendritic spines

Correct Answer: Ellman’s colorimetric assay

Q5. Which behavioral test is most sensitive for assessing spatial learning and memory deficits in rodent models of Alzheimer’s disease?

• Morris water maze
• Open field locomotion
• Rotarod performance
• Forced swim test

Correct Answer: Morris water maze

Q6. Which biomarker panel in cerebrospinal fluid (CSF) is classically used to support Alzheimer’s disease diagnosis and to evaluate target engagement in drug studies?

• Decreased Aβ42, increased total tau, increased phosphorylated tau
• Increased Aβ42, decreased total tau, decreased phosphorylated tau
• Increased α-synuclein, decreased Aβ42, decreased tau
• Increased dopamine, increased glutamate, decreased GABA

Correct Answer: Decreased Aβ42, increased total tau, increased phosphorylated tau

Q7. Which in vitro cell model is commonly used to study dopaminergic neuron biology and screening of neuroprotective compounds for Parkinson’s disease?

• SH-SY5Y neuroblastoma cells differentiated toward dopaminergic phenotype
• HEK293 kidney cells
• RAW264.7 macrophage line
• HepG2 hepatocyte cell line

Correct Answer: SH-SY5Y neuroblastoma cells differentiated toward dopaminergic phenotype

Q8. Which assay is frequently used to quantify soluble oligomeric forms of amyloid-beta in biological samples during drug screening?

• Oligomer-specific ELISA
• Comet assay for DNA damage
• Luxol fast blue staining
• Patch-clamp electrophysiology

Correct Answer: Oligomer-specific ELISA

Q9. What is the primary advantage of organotypic hippocampal slice cultures in Alzheimer’s drug screening compared with dissociated neuronal cultures?

• Preservation of native synaptic architecture and network connectivity
• Higher throughput than biochemical assays
• Better suitability for systemic pharmacokinetics
• Lower cost than immortalized cell lines

Correct Answer: Preservation of native synaptic architecture and network connectivity

Q10. Which imaging ligand is used with PET to visualize fibrillar amyloid plaques in vivo for translational efficacy studies?

• Pittsburgh compound B (PiB)
]Fluorodeoxyglucose (FDG)
• [^18F]DOPA
• 99mTc-HMPAO

Correct Answer: Pittsburgh compound B (PiB)

Q11. In Parkinson’s disease drug screening, the cylinder test primarily measures which functional endpoint in unilateral 6-OHDA lesioned rodents?

• Forelimb use asymmetry
• Spatial memory retrieval
• Anxiety-related behavior
• Olfactory discrimination

Correct Answer: Forelimb use asymmetry

Q12. Which assay would you use to assess compound effects on tau phosphorylation in a cell-based Alzheimer’s screening cascade?

• Western blot or ELISA for phospho-tau epitopes (e.g., pSer202/pThr205)
• Thioflavin T fluorescence
• Acetylcholine esterase activity
• Tyrosine hydroxylase immunostaining

Correct Answer: Western blot or ELISA for phospho-tau epitopes (e.g., pSer202/pThr205)

Q13. Which cell-based readout is commonly included to evaluate mitochondrial dysfunction as a screening endpoint for neurodegenerative disease therapeutics?

• Seahorse extracellular flux analysis (OCR/ECAR)
• Luciferase reporter gene activity
• Alkaline comet tail length
• Hoechst nuclear staining alone

Correct Answer: Seahorse extracellular flux analysis (OCR/ECAR)

Q14. For screening blood-brain barrier (BBB) permeability of candidate CNS drugs, which in vitro model provides a multicellular, higher-fidelity barrier compared with monolayer endothelial cultures?

• Human induced pluripotent stem cell (iPSC)-derived neurovascular unit co-culture
• Single-layer Caco-2 cell monolayer
• HEK293 overexpressing P-glycoprotein
• Primary hepatocyte sandwich culture

Correct Answer: Human induced pluripotent stem cell (iPSC)-derived neurovascular unit co-culture

Q15. Which assay can detect seeding activity of misfolded α-synuclein and is useful for PD biomarker and therapeutic screening?

• RT-QuIC (real-time quaking-induced conversion)
• ELISPOT for cytokine release
• Neutral red uptake assay
• Flow cytometric calcium flux

Correct Answer: RT-QuIC (real-time quaking-induced conversion)

Q16. When performing high-throughput screening (HTS) for inhibitors of amyloid aggregation, which parameter is critical to reduce false positives caused by compound fluorescence or quenching?

• Counter-screen using orthogonal non-fluorescent assay (e.g., mass spectrometry or filter trap)
• Increasing compound concentration beyond solubility limits
• Excluding all compounds with any aromatic groups
• Only screening in whole-animal models

Correct Answer: Counter-screen using orthogonal non-fluorescent assay (e.g., mass spectrometry or filter trap)

Q17. Which electrophysiological measure in hippocampal slices is commonly used to assess synaptic plasticity relevant to cognitive function in Alzheimer’s studies?

• Long-term potentiation (LTP) recorded as increased field EPSP slope
• Resting membrane potential of astrocytes
• Cardiac action potential duration
• Compound muscle action potential amplitude

Correct Answer: Long-term potentiation (LTP) recorded as increased field EPSP slope

Q18. Which assay is appropriate to screen anti-inflammatory effects of candidate compounds on microglial activation in neurodegenerative disease models?

• Measurement of nitric oxide production and proinflammatory cytokines (e.g., TNF-α, IL-1β) from activated microglia
• Albumin secretion from hepatocytes
• Insulin release from pancreatic islets
• Creatine kinase release from myotubes

Correct Answer: Measurement of nitric oxide production and proinflammatory cytokines (e.g., TNF-α, IL-1β) from activated microglia

Q19. In preclinical efficacy studies for Alzheimer’s disease, which endpoint best reflects restoration of synaptic integrity rather than simply reduction of amyloid load?

• Increased synaptophysin or PSD-95 immunoreactivity and improved LTP
• Decreased body weight
• Reduction in peripheral inflammatory markers only
• Lower liver enzyme levels

Correct Answer: Increased synaptophysin or PSD-95 immunoreactivity and improved LTP

Q20. Which pharmacokinetic/pharmacodynamic (PK/PD) consideration is most critical when interpreting translatable efficacy of a CNS drug candidate from rodent models to humans?

• Brain exposure (brain-to-plasma ratio) and target occupancy at efficacious dose
• Renal clearance in rodents only
• Compound color and odor
• Manufacturer’s recommendation for mouse bedding

Correct Answer: Brain exposure (brain-to-plasma ratio) and target occupancy at efficacious dose

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