Seminars Flashcards

1
Q

What is Alzheimer’s disease?

A

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%)

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2
Q

What’s the main risk factor for AD?

A

Age

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3
Q

How does AD present on a PET scan

A

Brain regions affected shrink (can lose up to 30% Brain mass) and a PET scan shows glucose utilisation (little activity in areas affected)

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4
Q

Name the two neyropathilogical hallmarks of AD

A

Amyloid plaques

Neurofibrillary tangles

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5
Q

Amyloid plaques consist of what protein fragment and what is the precursor of this protein?

A

Beta-amyloid

Amyloid precursor protein

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6
Q

Neurofibrillary tangles in AD consist of what?

A

Tau - a protein normally involved in maintaining the internal structure of the nerve cell

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7
Q

Is AD inherited?

A

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

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8
Q

In AD what is presenilin?

A

Part of an enzyme complex that cleaves APP to produce amyloid plaques

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9
Q

Why do downs patients present with AD at early age (40)?

A

Because they have an extra copy of chromosome 21 which is where the gene for APP is found

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10
Q

Name 3 genes that present a minor risk for developing AD

A

Clusterin
PICALM
TREM2

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11
Q

A copy of what allele can increase the risk of getting AD by four?

A

ApoE4

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12
Q

Where does the pathology of AD first appear?

A

In the entorhinal cortex (involved in memory and navigation)

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13
Q

What is the main neurotransmitter in the AD brain that is reduced due to loss of cholinergic nerve terminals in the entorhinal cortex?

A

Acetylcholine!

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14
Q

In the cholinergic terminal, what enzyme converts choline + acetyl coA into acetylcholine within the presynaptic cell?

A

Choline acetyltransferase (ChAT)

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15
Q

In the synapse of the cholinergic terminal, what enzyme converts ACh into choline and acetic acid?

A

Acetylcholinesterase (AChE)

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16
Q

Name three AChE inhibitors use in mild to moderate Alzheimer’s

A

Donepezil
Rivastigmine
Galantamine

17
Q

Name an NMDA receptor antagonist used in AD

A

Memantine

18
Q

Why have they tried NMDA receptor antagonists in AD?

A

To reduce background noise of glutamate –> thought that damaged cells release excess glutamate in AD

19
Q

Name a y-secretase inhibitor that failed in phase 3 trials

A

Semagacestat

20
Q

Name three beta-secretase inhibitors

A

Verubecestat
AZD3293
Janssen

21
Q

Name three theories for the use of anti-AB antibodies in AD

A

Plaque breakdown
Peripheral sink
Aggregation inhibitor

22
Q

Name two routes of the antibody strategy vaccine

A

1) active immunisation: immunisation with intact AB42 peptide or AB fragments
2) passive immunisation: immunisations with AB antibodies

23
Q

What is ADHD?

A

A medical condition characterised by inattention and/or hyperactivity/impulsivity

24
Q

ADHD is characterised by what three dimensions of behaviour?

A

Inattention
Impulsiveness
Hyperactivity

25
Q

Is ADHD highly heritable?

A

YEH

26
Q

In ADHD what two modern techniques have been used to investigate the neuroanatomical loci of the brain dysfunction?

A

Position emission tomography (PET) and functional magnetic resonance imaging (fMRI)

27
Q

Name two noradrenaline selective ADHD drugs

A

Atomoxetine

Guanfacine

28
Q

Name three ADHD drugs that effect both NA and DA neurotransmitters

A

Methylphenidate
Amphetamine
Lisdexamfetamine

29
Q

Name an ADHD drug that effects DA only

A

Bupropion

30
Q

Name two monoamine reuptake inhibitors used in ADHD

A

Atomoxetine

Bupropion

31
Q

Name a monoamine releasing agent used in ADHD

A

Amphetamines

32
Q

Name a psychostimulant reuptake inhibitor used in ADHD

A

Methylphenidate

33
Q

Name an alpha 2 adrenoceptor agonist used in ADHD

A

Guanfacine

34
Q

What is lisdexamfetamine?

A

It’s a d-amphetamine prodrug used in ADHD

35
Q

How is lisdexamfetamine activated?

A

Cleaved by RBC in a rate-limited enzymatic hydrolysis