Seminars Flashcards
(35 cards)
What is Alzheimer’s disease?
AD is the progressive brain disorder that gradually destroys a persons memory and ability to learn, reason and make judgements. It’s is the leading cause of dementia (75%)
What’s the main risk factor for AD?
Age
How does AD present on a PET scan
Brain regions affected shrink (can lose up to 30% Brain mass) and a PET scan shows glucose utilisation (little activity in areas affected)
Name the two neyropathilogical hallmarks of AD
Amyloid plaques
Neurofibrillary tangles
Amyloid plaques consist of what protein fragment and what is the precursor of this protein?
Beta-amyloid
Amyloid precursor protein
Neurofibrillary tangles in AD consist of what?
Tau - a protein normally involved in maintaining the internal structure of the nerve cell
Is AD inherited?
Not strongly - only small % inherited in early onset AD (25-61years) due to rare autosomal dominant mutations in:
1) amyloid precursor protein
2) presenilin 1 and presenilin 2
In AD what is presenilin?
Part of an enzyme complex that cleaves APP to produce amyloid plaques
Why do downs patients present with AD at early age (40)?
Because they have an extra copy of chromosome 21 which is where the gene for APP is found
Name 3 genes that present a minor risk for developing AD
Clusterin
PICALM
TREM2
A copy of what allele can increase the risk of getting AD by four?
ApoE4
Where does the pathology of AD first appear?
In the entorhinal cortex (involved in memory and navigation)
What is the main neurotransmitter in the AD brain that is reduced due to loss of cholinergic nerve terminals in the entorhinal cortex?
Acetylcholine!
In the cholinergic terminal, what enzyme converts choline + acetyl coA into acetylcholine within the presynaptic cell?
Choline acetyltransferase (ChAT)
In the synapse of the cholinergic terminal, what enzyme converts ACh into choline and acetic acid?
Acetylcholinesterase (AChE)
Name three AChE inhibitors use in mild to moderate Alzheimer’s
Donepezil
Rivastigmine
Galantamine
Name an NMDA receptor antagonist used in AD
Memantine
Why have they tried NMDA receptor antagonists in AD?
To reduce background noise of glutamate –> thought that damaged cells release excess glutamate in AD
Name a y-secretase inhibitor that failed in phase 3 trials
Semagacestat
Name three beta-secretase inhibitors
Verubecestat
AZD3293
Janssen
Name three theories for the use of anti-AB antibodies in AD
Plaque breakdown
Peripheral sink
Aggregation inhibitor
Name two routes of the antibody strategy vaccine
1) active immunisation: immunisation with intact AB42 peptide or AB fragments
2) passive immunisation: immunisations with AB antibodies
What is ADHD?
A medical condition characterised by inattention and/or hyperactivity/impulsivity
ADHD is characterised by what three dimensions of behaviour?
Inattention
Impulsiveness
Hyperactivity
