Alzheimers Flashcards
Name 5 symptoms of Alzheimers
1) Memory loss, especially recently acquired information. 2) Disorientation. 3) Poor judgement. 4) Language problems. 5) Personality changes.
Describe the amyloid hypothesis
Physiologically, APP (membrane protein throughout the brain) is cleaved by a-secretase forming sAPP-a and C83. C83 is digested by gamma-secretase and the products are removed. In Alzheimer’s its hypostehstis that the APP is cleaved by B-secretase forming s-APP-B forming a C99. When this is digested by gamma-secretase, it release B-amyloid protein.
B-amyloid proteins forms toxic aggregates that dopsit on neuronal cell surfaces as plaques and cause neuronal cell death.
Describe the tau hypothesis
Physiologically, tau is a soluble protein that is important in the assembly and stability of microtubules.
In Alzheimer’s these proteins get hyperphosphorylated and self-aggregate to form neurofibrillary tangles.They dissociate from the microtubules, causing instability as well as being directly neurotoxic.
Describe the microglia hypothesis
Microglia are specialised CNS immune cells, similar to macrophages. In Alzheimers, they increase release of inflammatory mediators and cytotoxic proteins, increase phagocytosis and decrease levels of neurotoxic proteins.
What are the two main classes of drugs used for Alzheimer’s disease?
Anticholinesterases and NMDA receptor blockers
What is donepezil?
A revsible cholinesterase inhibitor with a long half life
What is rivastigmine?
A pseudo-revesible AchE and BchE inhibitor. Only 8 hour half lfie but recently been reformulated as a transdermal patch.
What is galatamine?
A reversible chhilnestrase inhibitor as well as pecifically a a7 nACh RECEPTOR agonist. Hlaf life 7-8 hours.
What is Memantine and what is it prescribed for?
USE-DEPENDENT, NON-COMPETITIVE NMDA receptor BLOCKER. Low channel affinity .
Long plasma half life.
ONLY liscensed for MOD-SEVERE Alzheimer’s.
