Cycle 9 Flashcards
Q: What type of disease is Alzheimer’s Disease (AD)?
A: AD is a neurodegenerative disease, meaning it involves the loss or deterioration of neurons.
Q: Is AD a progressive disease?
A: Yes, AD progresses in one direction and cannot be reversed, treated, or cured like some other diseases (e.g., cancer).
Q: Where does neuron deterioration start in AD?
A: It starts in the hippocampus, which is responsible for memory storage and retrieval.
Q: What is the number one cause of dementia?
A: Alzheimer’s Disease (AD) is the leading cause of dementia, but having dementia does not necessarily mean someone has AD.
Q: How does the progression speed of AD vary?
A: It depends on both environmental factors and genetic predisposition.
Q: What are the two types of AD?
Early-onset AD (ages 30-50): Mostly genetically inherited.
Late-onset AD (past 65): Due to genetic factors + accumulation of mutations over time.
Q: What are the three main pathological hallmarks of AD?
1) Deterioration of cholinergic neurons (important for memory & learning).
2) Formation of plaques (due to APP deregulation).
3) Formation of tangles (Tau protein hyperphosphorylation)
Q: How do neurons communicate?
A: Neurons communicate via synapses, where neurotransmitters are released by the presynaptic neuron and received by the postsynaptic neuron.
Q: What neurotransmitter is involved in memory?
A: Acetylcholine (ACh), produced by cholinergic neurons.
Q: How is acetylcholine produced?
1) Choline + Acetyl-CoA → Acetylcholine (via Choline Acetyltransferase (CAT)).
2) Acetylcholine is released and binds to receptors on the postsynaptic neuron.
3) It is then broken down by Acetylcholinesterase (AChE) to prevent overstimulation.
Q: What happens to acetylcholine levels in AD?
A: Due to dysfunctional Choline Acetyltransferase (CAT), there is low acetylcholine production, leading to memory impairment.
Q: What is Amyloid Precursor Protein (APP)?
A: APP is a normal membrane protein involved in neuron function but must be properly recycled.
Q: What is the target for drug treatment?
A: Acetylcholinesterase inhibitors are used to prevent acetylcholine breakdown, keeping it in the synapse longer.
Q: How is APP normally processed? (2 paths)
Pathway 1: Alpha-secretase cuts → Gamma-secretase cuts → Soluble fragments → No plaque formation.
Pathway 2: Beta-secretase cuts → Gamma-secretase cuts → Amyloid-beta peptides formed (potential for plaque formation).
Q: What causes plaques in AD?
A: Overproduction & poor clearance of 42-amino acid amyloid-beta peptides, which are sticky and form aggregates outside neurons.
Q: What are the effects of plaques?
1) Block synapses, preventing neurotransmission.
2) Trigger immune response, causing inflammation and further neuronal damage.
3) Overproduce glutamate, leading to neuron overstimulation & death.
Q: What drugs target plaque-related neurodegeneration?
A: NMDA antagonists, which block the NMDA receptor to prevent neuron death from excessive glutamate stimulation.
Q: What is Tau protein’s normal function?
A: Tau helps stabilize microtubules (structural components in axons).
Q: What happens to Tau in AD?
1) Hyperphosphorylation causes Tau to detach from microtubules, leading to axon collapse.
2) Detached Tau forms tangles, further damaging neurons.
Q: Why are individuals with Down Syndrome at a higher risk for AD?
APP gene is on chromosome 21.
Trisomy 21 (extra chromosome 21) leads to more APP expression, increasing the risk of AD.
Q: What is the main focus of Alzheimer’s drug development?
Q: What is the main focus of Alzheimer’s drug development?
Q: What mutations are linked to familial AD?
1) Presenilin 1 & 2 mutations → Mutant gamma-secretase produces more 42-AA amyloid-beta peptides, increasing plaque formation.
2) Apolipoprotein E (ApoE) variants:
ApoE3 (common, neutral).
ApoE4 (poor at clearing amyloid-beta; autosomal dominant).
ApoE4 homozygotes (2 copies) → 12x higher risk of AD.
❓ What is the difference between inter-tumoral and intra-tumoral heterogeneity?
✅ Inter-tumoral heterogeneity: Differences between tumors from different individuals.
✅ Intra-tumoral heterogeneity: Differences between cells within the same tumor.
❓ How does cancer evolve over time?
✅ Cancer originates from a single mutated cell (clone).
✅ Successive mutations provide a growth advantage.
✅ The tumor becomes more aggressive with additional mutations.
