Alzheimer's Disease Flashcards
Main risk factor for Alzheimers?
Age
What protein leads to early stage Alzheimers?
amyloid precursor protein
What gene leads to early stage Alzheimers
PSEN
What gene leads to late stage Alzheimers
ApoE
Symptoms of Alzheimers? (5)
- Memory loss – especially recently acquired information
- Disorientation/ confusion – forgetting where they are
- Language problems – stopping in the middle of a conversation
- Personality changes – becoming confused, fearful, anxious
- Poor judgement – such as when dealing with money
What is the normal physiological processing of amyloid precursor protein (4)
- Amyloid precursor protein (APP) cleaved by a-secretase
- sAPPa (secretedAPPα) released - C83 fragment remains
- C83 is digested by gamma-secretase
- Products removed
What protein physiologically cleaves Amyloid precursor protein
alpha secretase
What protein pathophysiologically cleaves Amyloid precursor protein
Beta-secretase
What does physiologically cleavage of Amyloid precursor protein release
sAPPalpha and C83
What is the pathophysiological processing of Amyloid precursor protein (4)
- APP cleaved by b-secretase
- sAPPbeta released - C99 fragment remains
- C99 digested by g-secretase releasing b-amyloid (Ab) protein
- beta-amyloid forms toxic aggregates into dimers trimers etc, causing plaques to form on the neuronal cells which leads to neuronal cell deaths.
What does pathophysiological cleavage of Amyloid precursor protein release
sAPPbeta and C99
How does beta-amyloid form plaques
beta-amyloid forms toxic aggregates into dimers trimers etc, causing plaques to form on the neuronal cells which leads to neuronal cell deaths.
What is tau protein, where’s it found
- Tau protein is a soluble protein present in microtubules in axons
What is the function of tau protein
- Important for assembly & stability of microtubules which themselves are important for transportation of substances from the cell body to the presynaptic terminal
When is tau bad? (3)
- Hyper-phosphorylated tau is insoluble self-aggregates to form neurofibrillary tangles
- These are neurotoxic
- This is because it results in microtubule instability
Why is hyperphosphorylated tau forming tangles bad
Because it results in microtubule instability
What do microglia do?
Specialised CNS immune cells - similar to macrophages
What is the pathophysiology of microglia regarding Alzheimers (3)
- Increased release of inflammatory mediators & cytotoxic proteins
- Increased phagocytosis
- Decreased levels of neuroprotective proteins
Whatre the three main Alzheimers hypotheses
Tau hypothesis, beta amyloid hypothesis and the microglia hypothesis
What 2 classes of drugs are used to treat alzheimers
Anticholinesterases and NMDA receptor blockers
Example of 3 anticholinesterases used to treat Alzheimers?
Donepezil
Rivastigmine
Galantamine
What is donepezil used for
Alzheimers
What is rivastigmine used for
Alzheimers
What is galantamine used for
Alzheimers
