3. Alzheimer's

Question 1

What are the 4 anti Alzheimer’s drugs?

Answer 1

1. Donepezil
2. Galantamine
3. Memantine
4. Rivastigmine

Question 2

What is Alzheimer’s disease (AD)?

Answer 2

A neurodegenerative disorder of the elderly
Inflammation in the brain
Average life expectancy after diagnosis is 7 years
Shrinks cortex of brain, most of white matter tracts stay in tact
Diffuse cortical atrophy
High density of plaques and tangled in the frontal and temporal cortices

Slide 7-8

Question 3

What are the symptoms of Alzheimer’s disease?

Answer 3

Dementia:
Short term memory loss
Impaired memory retrieval
Can’t generate ideas and can’t manipulate concepts mentally
Impaired judgement and evaluation
Labile (easily altered mood) and inappropriate emotions

Motor functions are generally intact until late stages of disease

Slide 5

Question 4

What is the total affect of Alzheimer’s on the brain? (Neuropathology)

Answer 4

Diffuse cortical atrophy
Loss of cholinergic neurons in the nucleus basalis of Meynert that project to the frontal cortex
Loss of locus coeruleus neurons (also in Parkinson’s) may even precede nBM loss
Neurodegenerative starts many years before symptoms
Loss of LC and nBM neurons (summary)

Question 5

What are the 3 enzymes that affect Alzheimer’s?

Answer 5

α-secretase (ADAM10/TACE)
β-secretase (BACE)
γ-secretase

sAPPα- neuro-protective, promotes neurite outgrowth and synaptogenesis, enhances learning and memory
sAPPβ- stimulates axonal pruning and neuronal cell death

Slide 9

Question 6

What is the rate limiting pathway for Alzheimer’s?

Answer 6

β-secretase

Question 7

What is acetylcholine treatment therapy for Alzheimer’s?

Answer 7

ACh deficiency in Alzheimer’s patients
Acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine)
Inhibit acetylcholinesterase and ACh accumulates in brain

Question 8

What are anti-β-amyloid drugs affect on Alzheimer’s?

Answer 8

Valproic acid reduces/prevents formation of β-amyloid deposits in mice with AD
Pioglitazone shown to stim amyloid clearance and reversal of cognitive deficits in mouse models of AD

Question 9

How does anti-oxidant therapy help Alzheimer’s?

Answer 9

In vitro, antioxidants block the neurotoxicity of β-amyloid
Only 1 clinical trial published
Similar neurotoxic mechanisms seem to be at work in head trauma, stroke, Parkinson’s, Alzheimer’s and more
Vitamin E, C, blueberries, strawberries, ethanol

Question 10

Look at case study slide 19

Answer 10

Ok