Neurodegenerative Diseases Flashcards
Alzheimer’s disease causes what
Dementia and problems with: memory, language, judgement, thinking, personality, and perception
Prevalence of AD
5% at 65
>90% at 95
When early and late onset AD show
Before 60 (genetic)
After 60
Pathology ad
Decreased brain size from neuronal death and protein aggregation
AD: deficits in __ signaling due to what
Where this affects brain
Cholinergic, cholinergic neuron loss
Hippocampus (memory and learning) and frontal cortex (executive function)
AD has decreases in what on cellular level
- choline acetyltransferase activity
- acetylcholine amount
- acetylcholinesterases
- choline transport
- nicotinic acetylcholine receptor expression
2 current drug tx for AD
Cholinesterase inhibitors
NMDA receptor antagonist
Protein aggregates in AD caused by what
Amyloid plaques- amyloid beta
Neurofibrillary tangles- hyperphosphorylated tau
What happens in non amyloidogenic pathway
APP protein cleaved by a-secretase followed by y secretase
No Ab formed
What happens in amyloidogenic pathway
APP cleaved by b secretase followed by y secretase
Ab 40/42 aggregates form plaques
Effects of AB plaques
Unclear. Most likely to be soluble Ab derivatives from plaques that cause cognitive defects rather than plaques themselves
Genetic effects that can lead to early AD
Mutations that increase amounts of Ab
What is tau protein
What happens to it in AD
In Microtubules in normal neurons
Hyperphosphorylated in AD, cant support microtubules. Proteins form neurofibrillary tangles, correlates w neuronal death
Potential new drug targets for AD
Ab: block synthesis, promote clearance, block plaque formation
Tau: block aggregation
What Parkinson’s is
Movement disorder mainly in elderly, no obvious cause, genetic RF
What Parkinson’s is characterized by
Dyskinesias (difficulty starting/stopping movement)
Muscle rigidity
Tremor at rest
Cognitive impairments, depression
Where PD affects brain and function of this area
Basal ganglia: starts purposeful movement and suppressed unwanted movement
Striatum, globus pallidus, subthalamic nuclei, substantia Nigra
What normal function is in basal ganglia vs in pd
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
What levodopa is broken down by
Decarboxylases (DDC) and catecholamine o methyl transferase (COMT)
Dopamine doesnt do what
Cross BBB
What happens if levodopa taken alone
Even with large doses only a small amount will reach the brain. Large amounts can cause problems in periphery
Solution to making levodopa reach target better
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
PD pathology
Lewy bodies- misfolded alpha synuclein. Physio func of alpha syn is synaptic vesicle recycling
Process of developing PD
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
