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Neuroscience 2 > Neuropathology of Alzheimer's Disease > Flashcards

Neuropathology of Alzheimer's Disease Flashcards

Identify the key neuropathological features of AD Compare and contrast the cholinergic and amyloid cascade hypotheses Evaluate the methods being developed to assess brain pathology and to confirm the diagnosis of AD in living patients Discuss the utility of post-mortem examination as an end point in clinical trials

1
Q

What is the prevalence of Alzheimer’s disease in the 65-69 age group?

A

1.3%

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2
Q

What is the prevalence of Alzheimer’s disease in the 85-89 age group?

A

20.3%

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3
Q

Describe the 4 histopathological hallmarks of Alzheimer’s disease

A

Extracellular plaques, neurofibrillary tangles, cerebral amyloid angiopathy, neuronal loss

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4
Q

In which lobes of the brain is cerebral atrophy most pronounced in AD?

A

Frontal and temporal lobes

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5
Q

Describe the basis of the cholinergic hypothesis of AD

A

ACh turnover decreases with age, and a lack of ACh causes amnesia. A decrease in cholinergic markers appears to correlate with the clinical severity of dementia

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6
Q

Give three classes of drugs available to treat AD

A

Anti-cholinesterases, nicotinic receptor agonists, and glutamate antagonists

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7
Q

Name 2 anti-cholinesterases available to treat AD

A

Rivastigmine, donepezil, tacrine

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8
Q

Name a nicotinic receptor agonist available to treat AD

A

Galantamine

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9
Q

Name a glutamate antagonist available to treat AD

A

Memantine

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10
Q

Which type of dementia is memantine primarily used to treat?

A

Vascular dementia

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11
Q

What are neurofibrillary tangles?

A

Paired helical filaments of the microtubule associated protein tau, due to hyperphosphorylation of tau

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12
Q

Describe the classical appearance of extracellular plaques on immunostaining

A

A bullseye

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13
Q

Name two pathological features created by amyloid-beta

A

Extracellular (senile) plaques and cerebral amyloid angiopathy

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14
Q

Which protein is Alzheimer’s disease staged by - amyloid-beta or tau?

A

Tau

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15
Q

Which four areas of the brain are involved in the Braak staining of AD?

A

Anterior hippocampus, posterior hippocampus, temporal cortex, occipital cortex

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16
Q

Which area of the brain is affected by pathology first (Braak stage I)?

A

Transentorhinal region in the anterior hippocampus

17
Q

Which region of the brain is affected in Braak stage II?

A

Entorhinal region in the anterior hippocampus

18
Q

Which region of the brain is affected in Braak stage III?

A

Temporo-occipital gyrus in the posterior hippocampus, in addition to the entire anterior temporal lobe (entorhinal cortex)

19
Q

Which region of the brain is affected in Braak stage IV?

A

Temporal cortex. Symptoms now become clinically relevant

20
Q

Which region of the brain is affected in Braak stage V?

A

Peristriatal cortex in the occipital cortex

21
Q

Which region of the brain is affected in Braak stage VI?

A

Striatal cortex in the occipital cortex

22
Q

At which Braak stage do symptoms become clinically relevant?

A

IV (4)

23
Q

Define amyloid

A

A general ter, for any aggregate of peptide protein

24
Q

What is amyloid precursor protein?

A

A membrane-bound glycoprotein with a long extracellular amino acid and a short intracellular carboxy terminus

25
Q

Describe the difference between normal and pathological processing of APP

A

In normal processing, APP is cleaved by alpha-secretase at the amyloid-beta terminus. In pathological processing, APP is cleaved by beta-secretase, allowing cleavage by gamma secretase to produce amyloid-beta - which tends to form a beta-pleated sheet structure and aggregate

26
Q

Give 5 risk factors for AD

A

Ageing, family history, Down’s syndrome, previous head trauma, Parkinson’s disease, APOE4 genotype

27
Q

Give 2 chromosomes which host mutations causing early onset familial AD

A

Chromosome 14 and chromosome 21

28
Q

Which chromosome is the APP gene located on?

A

Chromosome 21

29
Q

Why is it theorised that individuals with Down’s syndrome develop AD?

A

They have an extra copy of chromosome 21, which carries the APP gene - the extra copy seems to lead to AD via mass effect

30
Q

Which gene is most commonly mutated in early-onset familial AD?

A

The gene encoding presenilin

31
Q

What is presenilin>

A

An integral membrane protein with roles in intracellular signalling and the determination of cell fate

32
Q

Which chromosome is apolipoprotein E encoded for on?

A

Chromosome 19

33
Q

How many alleles does apolipoprotein E have?

A

3

34
Q

How much does APOE4 increase the risk of AD?

A

2x in heterozygotes, 10x in homozygotes

35
Q

What is the function of apolipoprotein E?

A

It is involved in lipid metabolism and membrane repair

Neuroscience 2 (30 decks)

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