Alzheimer’s Disease – What goes wrong in the brain?

Question 1

Difference between alzheimers and depression:

Answer 1

Alzheimer’s neurodegenerative, depression is neuropsychiatric

Question 2

What is Alzheimer’s Disease?

Answer 2

Alzheimer’s Disease (AD) is probably the best–known cause of dementia, accounting for about two–thirds of cases in the elderly

It is a neurodegenerative disease leading the patient to a state of depersonalisation and complete dependence

Cognition – short and long term planning, attention etc
Memory impairments big indicator

Slow onset – sporadic – not necessarily a genetic link
Early onset – genetic – accumulation of amyloids
Tw

Question 3

Risk factors of AD:

Answer 3

• Age (biggest)
• Genetic inheritance,
• Lifestyle & general health
• Environmental factors

Question 4

Two main types of symptoms have been a focus for the treatment in dementia and related disorders

Answer 4

1. Cognitive Deficits
2. Non-cognitive features – just due to brain disfunction (Behavioural and Psychological Symptoms of Dementia [BPSD) consisting of affective, psychotic and behavioural disturbances

Depression, Psychosis, Agitation, Apathy, Insomnia, Sexual disinhibition…..

Up to 90% of people with dementia will develop BPSD at some point in their illness.

Increase in caregiver burden —- Precipitate institutionalisation —– cost of care —-

Question 5

What causes Alzheimer’s Disease?

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

Question 6

What are EOAD and LOAD:

Answer 6

EOAD = a lot of the genetic muatations result in exces APP do you get excess amyloid production

LOAD = clearance doesn’t seem to work well which is the issue = then you get increased stickiness = plaques

Question 7

The Amyloid Cascade Hypothesis:

Answer 7

• 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 8

What are the current treatments?

Answer 8

Cholinesterase inhibitors:
Donepezil (Aricept)
Rivastigmine (Exelon)
Galantamine (Reminyl)

Works by increasing the amount of acetylcholine which helps messages to travel around the brain however, don’t prevent disease progression.

Question 9

Novel treatments for Alzheimer’s Disease?

Answer 9

1) Secretase modulators (Decrease Aβ42 production).
Decreasing amyloid production – issues of getting drug into the BBB, bad side effects

2) Anti-aggregants (Prevent Aβ aggregation)
3) Immunotherapies (Clear Aβ deposition)

Question 10

How does Reveratrol, a chemical found in red wine, work:

Answer 10

Reveratrol binds to amyloid and chops it up

Resveratrol disrupts the binding of Aβ to nerve cells