Alzheimer's Disease Flashcards

1
Q

Main risk factor for Alzheimers?

A

Age

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2
Q

What protein leads to early stage Alzheimers?

A

amyloid precursor protein

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3
Q

What gene leads to early stage Alzheimers

A

PSEN

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4
Q

What gene leads to late stage Alzheimers

A

ApoE

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5
Q

Symptoms of Alzheimers? (5)

A
  • 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
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6
Q

What is the normal physiological processing of amyloid precursor protein (4)

A
  1. Amyloid precursor protein (APP) cleaved by a-secretase
  2. sAPPa (secretedAPPα) released - C83 fragment remains
  3. C83 is digested by gamma-secretase
  4. Products removed
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7
Q

What protein physiologically cleaves Amyloid precursor protein

A

alpha secretase

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8
Q

What protein pathophysiologically cleaves Amyloid precursor protein

A

Beta-secretase

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9
Q

What does physiologically cleavage of Amyloid precursor protein release

A

sAPPalpha and C83

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10
Q

What is the pathophysiological processing of Amyloid precursor protein (4)

A
  1. APP cleaved by b-secretase
  2. sAPPbeta released - C99 fragment remains
  3. C99 digested by g-secretase releasing b-amyloid (Ab) protein
  4. beta-amyloid forms toxic aggregates into dimers trimers etc, causing plaques to form on the neuronal cells which leads to neuronal cell deaths.
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11
Q

What does pathophysiological cleavage of Amyloid precursor protein release

A

sAPPbeta and C99

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12
Q

How does beta-amyloid form plaques

A

beta-amyloid forms toxic aggregates into dimers trimers etc, causing plaques to form on the neuronal cells which leads to neuronal cell deaths.

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13
Q

What is tau protein, where’s it found

A
  • Tau protein is a soluble protein present in microtubules in axons
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14
Q

What is the function of tau protein

A
  • Important for assembly & stability of microtubules which themselves are important for transportation of substances from the cell body to the presynaptic terminal
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15
Q

When is tau bad? (3)

A
  • Hyper-phosphorylated tau is insoluble self-aggregates to form neurofibrillary tangles
  • These are neurotoxic
  • This is because it results in microtubule instability
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16
Q

Why is hyperphosphorylated tau forming tangles bad

A

Because it results in microtubule instability

17
Q

What do microglia do?

A

Specialised CNS immune cells - similar to macrophages

18
Q

What is the pathophysiology of microglia regarding Alzheimers (3)

A
  • Increased release of inflammatory mediators & cytotoxic proteins
  • Increased phagocytosis
  • Decreased levels of neuroprotective proteins
19
Q

Whatre the three main Alzheimers hypotheses

A

Tau hypothesis, beta amyloid hypothesis and the microglia hypothesis

20
Q

What 2 classes of drugs are used to treat alzheimers

A

Anticholinesterases and NMDA receptor blockers

21
Q

Example of 3 anticholinesterases used to treat Alzheimers?

A

Donepezil
Rivastigmine
Galantamine

22
Q

What is donepezil used for

A

Alzheimers

23
Q

What is rivastigmine used for

A

Alzheimers

24
Q

What is galantamine used for

A

Alzheimers

25
Q

What family of drugs does Donepezil belong to

A

Anticholinesterase

26
Q

What family of drugs does Rivastigmine belong to

A

Anticholinesterase

27
Q

What family of drugs does Galantamine belong to

A

Anticholinesterase

28
Q

How long do the effects of Anticholinesterases work in alleviating symptoms of Alzheimers

A

about a year

29
Q

What can NMDA receptor blockers be used to treat?

A

Alzheimers

30
Q

What types of drugs were trialled for Alzheimers but failed?

A
  1. g-secretase inhibitors

2. b-amyloid antibody therapy