Unit 11 - Neurological Diseases

Question 1

What are plaques in the brain?

Answer 1

Insoluble deposits of a peptide called Abeta.

Question 2

How are plaques formed?

Answer 2

When a protein known as Amyloid Precursor Protein is cleaved by two enzymes known as Gamma Secretase and Beta Secretase.

Question 3

What happens after Amyloid Precursor Protein cleavage?

Answer 3

Abeta misfolds, becomes sticky, and clumps with others to form Oligomers. Oligomers clump together to form plaques.

Question 4

What is one negative function of Oligomers?

Answer 4

Weaken communication and plasticity at synapses.

Question 5

What are microglia?

Answer 5

Immune cells that clear out waste and prune synapses during development.

Question 6

Can microglia be affected by abeta?

Answer 6

Yes, Abeta can cause microglia to release cytokines which can damage neurons.

Question 7

What are some of the reasons the brain can’t store information properly?

Answer 7

Phagocytosis of synapses by microglia. Malfunction synapses and neuron death.

Question 8

What is Tau?

Answer 8

A protein that is a component of tangles. Stabilizes microtubules along axon.

Question 9

What happens when Tau is unstable?

Answer 9

The protein leaves the axon microtubules and this can cause the neuron to die. Tau can also spread and affect other healthy neurons.

Question 10

What is Alzheimers disease, and name the 3 types?

Answer 10

Irreversible progressive memory loss and thinking skill loss.

1) Sporadic nonhereditary
2) Early Onset Familial
3) Early Onset

Question 11

Alzheimers Incidence

Answer 11

21/100,000

Question 12

Alzheimers Evaluation

Answer 12

CT, MRI, PET, brain imaging.

Question 13

Besides plaque and Tau misregulation, what other reason may Alzheimers sporadically progress?

Answer 13

ApoE4 Protein. A lipoprotein responsible for Cholesterol metabolism. Protein can become truncated or shortened. This will destabilize the cytoskeleton in neuron. Impairs synapse communication.

Question 14

Alzheimers vs Age-Related Changes

Answer 14

Alzheimers -> Poor judgement, Can’t manage budget, Losing track of date, Difficult Conversations. Severity level.

Question 15

How do neuritic plaques form?

Answer 15

Proteolysis of the amyloid precursor protein and accumulation of B-amyloid

Question 16

What is ALS?

Answer 16

Amyotrophic Lateral Sclerosis - Neurogenetive disorder resulting in progressive muscle weakness. Sporadic.

Question 17

Why does ALS happen?

Answer 17

Exact Cause unknown. Sporadic but 4/100,000 people.

Question 18

What are symptoms of ALS?

Answer 18

Focal muscle weakness in legs/arms, muscle atrophy, loss of dexterity. Can be evaluated by EMG, muscle biopsy.

Question 19

What are some potential causes of ALS?

Answer 19

Excitotoxicity of glutamate
Mitochondrial dysfunction
Abnormal protein aggregation
Impaired axonal transport
Oxidative Stress (SOD1)
Neuroinflammation

Question 20

What is glutamate?

Answer 20

One of our neurotransmitters that helps to stimulate or cause an action potential and spread throughout the body.

Question 21

What is SOD1?

Answer 21

A gene that acts as an antioxidant. If mutated, oxidative stress around important organelles.

Question 22

What is glutamate excitotoxicity?

Answer 22

Excess glutamate around neuron to excite neuron when we don’t want it to be excited, hence muscle spasticity.

Question 23

What is myelin?

Answer 23

Protective sheath around axons of neurons. Produced by oligodendricytes.

Question 24

What happens with myelin in Multiple Sclerosis?

Answer 24

Immune system attacks myelin, causing communication breakdown.

Question 25

Environmental Factors for MS?

Answer 25

Infections, Vitamin D deficiency.

Question 26

Genetic Factors for MS?

Answer 26

Being Female | HLA-DR2 Gene

Question 27

What are the four types of MS?

Answer 27

1. RRMS Relapsing Remitting - Months or Years apart attacks. Line Stays flat in disability. 2. SPMS Secondary Progressive- Immune attack becomes constant. 3. PPMS Primary Progressive- One constant attack on myelin. Steady disability progression 4. PRMS - Progressive relapsing MS - One constant attack, superimposed bouts. Faster disability.

Question 28

What are they symptoms of MS of Charcot's neurological Triad?

Answer 28

1. Nystagmus - Involuntary eye movement - Plaque around eye nerves. 2. Dysarthria - Difficult Speech - Plaque around brainstem 3. Intention Tremor - Plaque along motor pathways.

Question 29

What are some other things plaque can do in regards to MS?

Answer 29

Plaques in sensory pathways cause skin tingles Plaques in autonomic nervous system Plaque leading to feelings of shock down back.

Question 30

MS Incidence

Answer 30

3/100,000

Question 31

How is MS started?

Answer 31

Our T and B cells recognize myelin as antigen, disrupts nerve conduction.

Question 32

Pathophysiology of MS?

Answer 32

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.

Question 33

How does T Cell attack myelin?

Answer 33

Myelin fragment presented to T cell with MHC Class II. | Cytokines released then more T-Cells called in.

Question 34

What is the differentiating feature in Parkinson's Disease?

Answer 34

``` Dopamine Defieciency (also oxidative stress, mitochondrial dysfunction, and reduction of nerve growth factors.) ```

Question 35

Pathophysiologically what are some distinguishing factors with Parkinson's?

Answer 35

Dopamine deficiency Oxidative Stress in Basal Ganglia Dopamine producing cells in Substantia Nigra Portion of brain.