Alzheimer's Flashcards
(30 cards)
What is Alzheimer’s disease?
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and impaired executive function. It is the most common cause of dementia and has no known cure.
What is the largest risk factor for developing Alzheimer’s disease?
Age is the strongest risk factor, with prevalence doubling every 5 years after age 65.
Which population has a higher risk of developing Alzheimer’s?
Women are more affected than men.
What is the estimated global economic cost of dementia as of 2017?
$818 billion, projected to reach $2 trillion by 2030.
What is the amyloid hypothesis in Alzheimer’s disease?
The amyloid hypothesis suggests that amyloid-beta (Aβ) accumulation is the primary trigger for Alzheimer’s pathology, leading to synaptic dysfunction, tau aggregation, and neuronal death.
What is amyloid precursor protein (APP) and how does it relate to Alzheimer’s?
APP is a transmembrane protein. When cleaved by β-secretase (BACE1) and γ-secretase, it produces Aβ1-42, the most toxic amyloid-beta variant that aggregates into plaques.
What is the key difference between the non-amyloidogenic and amyloidogenic pathways of APP cleavage?
• Non-amyloidogenic pathway: APP is cleaved by α-secretase, producing sAPPα, which is neuroprotective.
• Amyloidogenic pathway: APP is cleaved by β-secretase and γ-secretase, producing Aβ1-42, which forms toxic plaques.
What impact does BACE1 knockout have in experimental models?
While it reduces Aβ production, BACE1 knockout leads to hypomyelination, particularly in the optic nerve, and causes frequent epileptic seizures.
What are the main β-secretase inhibitors used in Alzheimer’s treatment research?
• Verubecestat (β-secretase 1 & 2 inhibitor)
• Lanabecestat (β-secretase 1 inhibitor)
• Atabecestat (β-secretase 1 inhibitor)
What is tau protein’s normal function?
Tau stabilizes microtubules, supporting axonal transport and neuronal integrity.
How does tau pathology contribute to Alzheimer’s disease?
In AD, tau becomes hyperphosphorylated, loses its microtubule-binding ability, and aggregates into neurofibrillary tangles (NFTs), disrupting neuronal function.
What types of tau filaments are found in Alzheimer’s disease?
• Paired helical filaments (PHFs) – Predominate in AD (~90%).
• Straight filaments (SFs)
What is the relationship between neurofibrillary tangles (NFTs) and Alzheimer’s progression?
The number of NFTs correlates strongly with disease severity and cognitive decline.
How does synaptic loss contribute to Alzheimer’s symptoms?
Synaptic loss leads to:
• Reduced dendritic branching
• Impaired synaptic plasticity
• Downregulation of key proteins like PSD-95 and drebrin, weakening signal transmission.
Which brain region shows the most significant synapse reduction in Alzheimer’s?
The stratum radiatum of the hippocampal CA1 region.
Which brain regions are most affected in early-stage Alzheimer’s?
The hippocampus and entorhinal cortex — regions essential for memory and spatial navigation.
Which brain regions are progressively affected as Alzheimer’s advances?
The frontal, parietal, and temporal lobes, impairing reasoning, language, and executive function.
What role do microglia play in Alzheimer’s?
• Early disease stage: Microglia are neuroprotective, clearing debris and dead cells.
• Late disease stage: Chronic activation leads to neurotoxic inflammation, releasing cytokines that worsen neuronal damage.
How do A1 and A2 astrocytes differ in Alzheimer’s disease?
• A1 Astrocytes: Neurotoxic, promote amyloid-beta production and neuronal death.
• A2 Astrocytes: Neuroprotective, supporting synaptic repair and neuron survival.
Which genetic variant is strongly linked to Alzheimer’s risk?
The APOE ε4 allele is a major risk factor.
What are other risk factors for Alzheimer’s?
• Cardiovascular disease (e.g., smoking, diabetes)
• Depression
• Head trauma
• Lack of exercise
What imaging techniques are used to diagnose Alzheimer’s?
• PET scans to detect Aβ plaque deposits
• MRI to observe brain atrophy
• CSF analysis to measure Aβ and tau levels.
What cognitive test is commonly used to assess Alzheimer’s symptoms?
The Mini-Mental State Exam (MMSE) evaluates cognitive impairment.
What are the main drug classes used to manage Alzheimer’s symptoms?
• Acetylcholinesterase inhibitors (e.g., donepezil, rivastigmine) — improve acetylcholine signaling.
• Memantine — an NMDA receptor antagonist that reduces glutamate excitotoxicity.
