Unit 11 - Neurological Diseases Flashcards
What are plaques in the brain?
Insoluble deposits of a peptide called Abeta.
How are plaques formed?
When a protein known as Amyloid Precursor Protein is cleaved by two enzymes known as Gamma Secretase and Beta Secretase.
What happens after Amyloid Precursor Protein cleavage?
Abeta misfolds, becomes sticky, and clumps with others to form Oligomers. Oligomers clump together to form plaques.
What is one negative function of Oligomers?
Weaken communication and plasticity at synapses.
What are microglia?
Immune cells that clear out waste and prune synapses during development.
Can microglia be affected by abeta?
Yes, Abeta can cause microglia to release cytokines which can damage neurons.
What are some of the reasons the brain can’t store information properly?
Phagocytosis of synapses by microglia. Malfunction synapses and neuron death.
What is Tau?
A protein that is a component of tangles. Stabilizes microtubules along axon.
What happens when Tau is unstable?
The protein leaves the axon microtubules and this can cause the neuron to die. Tau can also spread and affect other healthy neurons.
What is Alzheimers disease, and name the 3 types?
Irreversible progressive memory loss and thinking skill loss.
1) Sporadic nonhereditary
2) Early Onset Familial
3) Early Onset
Alzheimers Incidence
21/100,000
Alzheimers Evaluation
CT, MRI, PET, brain imaging.
Besides plaque and Tau misregulation, what other reason may Alzheimers sporadically progress?
ApoE4 Protein. A lipoprotein responsible for Cholesterol metabolism. Protein can become truncated or shortened. This will destabilize the cytoskeleton in neuron. Impairs synapse communication.
Alzheimers vs Age-Related Changes
Alzheimers -> Poor judgement, Can’t manage budget, Losing track of date, Difficult Conversations. Severity level.
How do neuritic plaques form?
Proteolysis of the amyloid precursor protein and accumulation of B-amyloid
What is ALS?
Amyotrophic Lateral Sclerosis - Neurogenetive disorder resulting in progressive muscle weakness. Sporadic.
Why does ALS happen?
Exact Cause unknown. Sporadic but 4/100,000 people.
What are symptoms of ALS?
Focal muscle weakness in legs/arms, muscle atrophy, loss of dexterity. Can be evaluated by EMG, muscle biopsy.
What are some potential causes of ALS?
Excitotoxicity of glutamate Mitochondrial dysfunction Abnormal protein aggregation Impaired axonal transport Oxidative Stress (SOD1) Neuroinflammation
What is glutamate?
One of our neurotransmitters that helps to stimulate or cause an action potential and spread throughout the body.
What is SOD1?
A gene that acts as an antioxidant. If mutated, oxidative stress around important organelles.
What is glutamate excitotoxicity?
Excess glutamate around neuron to excite neuron when we don’t want it to be excited, hence muscle spasticity.
What is myelin?
Protective sheath around axons of neurons. Produced by oligodendricytes.
What happens with myelin in Multiple Sclerosis?
Immune system attacks myelin, causing communication breakdown.
Environmental Factors for MS?
Infections, Vitamin D deficiency.
Genetic Factors for MS?
Being Female
HLA-DR2 Gene
What are the four types of MS?
- RRMS Relapsing Remitting - Months or Years apart attacks. Line Stays flat in disability.
- SPMS Secondary Progressive- Immune attack becomes constant.
- PPMS Primary Progressive- One constant attack on myelin. Steady disability progression
- PRMS - Progressive relapsing MS - One constant attack, superimposed bouts. Faster disability.
What are they symptoms of MS of Charcot’s neurological Triad?
- Nystagmus - Involuntary eye movement - Plaque around eye nerves.
- Dysarthria - Difficult Speech - Plaque around brainstem
- Intention Tremor - Plaque along motor pathways.
What are some other things plaque can do in regards to MS?
Plaques in sensory pathways cause skin tingles
Plaques in autonomic nervous system
Plaque leading to feelings of shock down back.
MS Incidence
3/100,000
How is MS started?
Our T and B cells recognize myelin as antigen, disrupts nerve conduction.
Pathophysiology of MS?
T-Cells cross blood brain barrier
T-Cells activated by myelin
More T-Cells enter.
T-Cells release cytokines and bring in more immune cells.
Myelinated oligodendrocytes destroyed by macrophages and T Cells.
Microglia assists by releasing macrophages to assist T-Cells.
Exposed axons disrupt nerve conduction.
How does T Cell attack myelin?
Myelin fragment presented to T cell with MHC Class II.
Cytokines released then more T-Cells called in.
What is the differentiating feature in Parkinson’s Disease?
Dopamine Defieciency (also oxidative stress, mitochondrial dysfunction, and reduction of nerve growth factors.)
Pathophysiologically what are some distinguishing factors with Parkinson’s?
Dopamine deficiency
Oxidative Stress in Basal Ganglia
Dopamine producing cells in Substantia Nigra Portion of brain.
