Alziemher's

Question 1

why are neurones dying?

Answer 1

• loss of synapses

- don’t get symptoms straight away as you cannot always see this loss

Question 2

what is alziemhers disease/

Answer 2

is probably the best–known cause of dementia, accounting for about two–thirds of cases in the elderly

Question 3

what are the risk factors fo AD?

Answer 3

§ Age  every 5 years from 65 years old you risk increase rapidly. But there is also early onset caused by genetic inheritance. Late onset is sporadic
§ Genetic inheritance  mutation causes and increase in the amyloid cascade
§ Lifestyle & general health
§ Environmental factors

Question 4

what are the two types of symptoms for dementia disorders?

Answer 4

1. Cognitive Deficits = loss of neurones start to see a memory impairment
2. Non-cognitive features (Behavioural and Psychological Symptoms of Dementia [BPSD) consisting of affective, psychotic and behavioural disturbances. More symptomatic and you have to treat the symptoms not the Alziemhers

Question 5

what causes AD?

Answer 5

§ During the course of the disease, two abnormal proteins build in the brain.
§ They form clumps called either ‘plaques’ or ‘tangles’.
- β Amyloid —- Plaques
- Tau —- Tangles

• We can do brain scans which would show the presence of amyloid. Amyloid is the starter for the cascade effect which activates Tau
• Tau keeps neurones stable but it can become hyperphosphated

Question 6

what can we target?

Answer 6

• We could target the production of the amyloid poylmers so they cannot agglomerate to produce a plaque. But this is very toxic and therefore could be too risky.
• Target and break down the plaques? This is less toxic to the neurones but failed tests for this
• Inhibit the b secretases? This has failed as it is needed in multiple process and could produce more side effects.
• Add an antibody which would stick to the oligomer and cause the immune system to pick it up an clear it – triggering an immune response

Question 7

why is is hard to treat?

Answer 7

it is hard to get drugs into the brain and this means treatment options are reduced

Question 8

what is the amyloid cascade hypothesis?

Answer 8

A generic aggregation scheme for amyloid-forming proteins. Proteins fold into their native structure, which is typically a low free energy configuration. However, the energy landscape for protein folding often can have localized minima in which a protein can become trapped into a misfolded conformation, which can lead to aggregation into β-sheet rich amyloid fibrils. The formation of fibrils often proceeds through a heterogeneous mixture of intermediate species, including oligmers and protofibrils. Off-pathway aggregates can also form, such as annular aggregates. These aggregates accumulate into amyloid plaques or inclusions in the diseased brain. The aggregation pathway for any given amyloid-forming protein can vary considerably depending on the protein and its folding environment.

Question 9

what are the current treatments for AD?

Answer 9

progression
Cholinesterase Inhibitors
- People with mild to moderate could benefit from this as it increase the amount of acetylcholine and this allows messages to travel around the brain
- Block the enzyme and increase the synaptic conc of AChE, this would help to improve the symptoms
- Should help the person function better

Question 10

what are examples of cholinesterase inhibitors?

Answer 10

Donepezil, Rivastigmine, Galantamine

Question 11

what are the more novel treatments of AD?

Answer 11

• Secretase modulators (decrease AB42 production) - bad side effects to these
• Anti-aggregants (prevent aggregation)- this works and targets to prevent the oligomers producing plaques. Hard to get into the brain
• Immunotherapies (clear AB) - this means you mark it with an antibody so that the immune system would clear it from the body and prevent them being able to aggregate and form plaques.
• All of the novel treatments need to be specific to the person/population you are giving them to or they won’t be successful.