Neurodegenerative Diseases

Question 1

Alzheimer’s disease causes what

Answer 1

Dementia and problems with: memory, language, judgement, thinking, personality, and perception

Question 2

Prevalence of AD

Answer 2

5% at 65

>90% at 95

Question 3

When early and late onset AD show

Answer 3

Before 60 (genetic)

After 60

Question 4

Pathology ad

Answer 4

Decreased brain size from neuronal death and protein aggregation

Question 5

AD: deficits in __ signaling due to what

Where this affects brain

Answer 5

Cholinergic, cholinergic neuron loss

Hippocampus (memory and learning) and frontal cortex (executive function)

Question 6

AD has decreases in what on cellular level

Answer 6

• choline acetyltransferase activity
• acetylcholine amount
• acetylcholinesterases
• choline transport
• nicotinic acetylcholine receptor expression

Question 7

2 current drug tx for AD

Answer 7

Cholinesterase inhibitors

NMDA receptor antagonist

Question 8

Protein aggregates in AD caused by what

Answer 8

Amyloid plaques- amyloid beta

Neurofibrillary tangles- hyperphosphorylated tau

Question 9

What happens in non amyloidogenic pathway

Answer 9

APP protein cleaved by a-secretase followed by y secretase

No Ab formed

Question 10

What happens in amyloidogenic pathway

Answer 10

APP cleaved by b secretase followed by y secretase

Ab 40/42 aggregates form plaques

Question 11

Effects of AB plaques

Answer 11

Unclear. Most likely to be soluble Ab derivatives from plaques that cause cognitive defects rather than plaques themselves

Question 12

Genetic effects that can lead to early AD

Answer 12

Mutations that increase amounts of Ab

Question 13

What is tau protein

What happens to it in AD

Answer 13

In Microtubules in normal neurons

Hyperphosphorylated in AD, cant support microtubules. Proteins form neurofibrillary tangles, correlates w neuronal death

Question 14

Potential new drug targets for AD

Answer 14

Ab: block synthesis, promote clearance, block plaque formation

Tau: block aggregation

Question 15

What Parkinson’s is

Answer 15

Movement disorder mainly in elderly, no obvious cause, genetic RF

Question 16

What Parkinson’s is characterized by

Answer 16

Dyskinesias (difficulty starting/stopping movement)
Muscle rigidity
Tremor at rest
Cognitive impairments, depression

Question 17

Where PD affects brain and function of this area

Answer 17

Basal ganglia: starts purposeful movement and suppressed unwanted movement

Striatum, globus pallidus, subthalamic nuclei, substantia Nigra

Question 18

What normal function is in basal ganglia vs in pd

Answer 18

Normal: dopamine and acetylcholine are balanced, controlled movement

Pd: reduced DA in striatum, imbalance between DA and ACh. 70% loss of dopamine neurons in substantia Nigra before symptoms appear

Question 19

What levodopa is broken down by

Answer 19

Decarboxylases (DDC) and catecholamine o methyl transferase (COMT)

Question 20

Dopamine doesnt do what

Answer 20

Cross BBB

Question 21

What happens if levodopa taken alone

Answer 21

Even with large doses only a small amount will reach the brain. Large amounts can cause problems in periphery

Question 22

Solution to making levodopa reach target better

Answer 22

Carbidopa taken w it (peripheral decarboxylase inhibitor) and entacapone (COMT inhibitor). Same amt levodopa can reach the brain w smaller dose. Entacapone added when effectiveness of levodopa/carbidopa wanes

Question 23

PD pathology

Answer 23

Lewy bodies- misfolded alpha synuclein. Physio func of alpha syn is synaptic vesicle recycling

Question 24

Process of developing PD

Answer 24

Misfolded alpha synuclein- loss of normal recycling func - deficit in vesicular storage of dopamine - increase in cytosolic dopamine - neurotoxicity d/t increase in reactive oxygen species