Memory 2 Flashcards
Which beta amyloid protein has a more severe effect?
Beta amyloid 42
What does intracellular Tau do?
Causes neuronal cell death
What can beta amyloid plaques form complexes with?
Metal ions–> Cu, Fe etc
What is produced as a result of beta amyloid plaques forming complexes with metal ions?
Peroxide
What can peroxide do in neurons?
Peroxidate membrane lipids
Effect of peroxidation on membrane lipids?
Can comprimise their functions–> functions of membrane spanning proteins
Examples of membrane spanning proteins on neurons
All ion channels, all NT receptors etc
What can happen if Ca2+ levels are too high in neurons?
Calcium sets off toxic events
What can calcium cause in neurons that is toxic?
Excitotoxicity, tau phosphorylation
What, other than peroxidation, can beta amyloid plaques cause?
Tau phosphorylation
What can tau phosphorylation (and thus neurofibrillary tangle formation) cause?
Disruption of microtubular transport
Main drugs used to treat AZ? symptoms?
Cholinesterase inhibitors, memantine, nootropics,
Examples of cholinesterase inhibitors?
Donepezil, rivastigmine, galangamine
Which type of NT neurons are first affected in AZ?
CHolinergic neurons
Role of Ach in entorhinal cortex and hippocampus?
LTP and normal function
Effect of cholinesterase inhibitors?
ACh stays in synapse for longer so more signalling to postsynaptic neuron
Which drug is given to people in later stage AZ?
Memantine
What is memantine?
Non-competitive NMDA receptor blocker
Why does memantine work as an AZ treatment?
Not known, may be neuroprotective
What a nootropics?
Drugs that are cognitive enhancers
What are AMPAkines?
Positive allosteric modulators at ampa receptor
What is used to treat ADHD?
Methylphenidate (ritalin)
Four drugs used to treat AZ?
Donepezil, rivastigmine, galantamine, memantine
What is most of the research about treating AZ progression aimed at?
The Beta Amyloid hypothesis
Which drugs targeting the beta amyloid hypothesis are in trials?
Beta secretase inhibitors, anti-amyloid beta vaccine/monoclonal antibodies, anti tau vaccine/monoclonal antibodies
How are copper and zinc targeted in possible AZ progression treatment?
With chelators as the metal ions can promote plaque formation
Issues with nerve growth factors for treating AZ?
Would have to be directly infused into brain so cant be used for routine therapy
Effect of statins on AZ?
Cholesterol promotes amyloid deposition, and statins can reduce cholesterol levels
What are donanemab and lecanemab?
Monoclonal antibodies against beta amyloid peptide–> prevent plaque formation by sticking too it
How effective are donanemab and lecanemab?
Delay progression by ~ 4 months
What can be used for early diagnosis?
Beta amyloid plaque formation–> can start to form 5-10 years before symptoms
What could be used to look for AZ biomarkers?
Blood samples, brain scans, spinal fluid draw (last two are difficult)
