Week 7: Path-degenerative and demyelinating diseases

Question 1

List the questions that should be asked in assessment, including laboratory and genetic tests, of a patient with possible Alzheimer disease, and the diagnostic utility of each.

Answer 1

1. neuro exam
2. mini mental status exam (normal 27+)
3. genetic test-ABO B gene
4. family hx
5. lab tests to rule out B12, e.g.

Question 2

Name 3 histological hallmarks of Alzheimer disease and the key corresponding proteins correlated with disease pathogenesis

Answer 2

1. neurofibrillary tangles - tau
2. neuritic plaques - ABeta amayloid
3. ?

Question 3

Describe how Pick disease exemplifies the molecular mechanisms resulting in tauopathies; especially the effects of alternative splicing of tau mRNA

Answer 3

• causes abnormal tau
• they aggregate in cytoplasm of neurons and cause inclusions
• occur in frontotemporal area

Question 4

Define the effects of extended triple codon repeats on the pathogenesis of Huntington disease.

Answer 4

The more repeats the more accelerated the disease. Occurs earlier and more severely.

Question 5

Define the neuronal system affected in Parkinson disease and how this is reflected clinically and pharmacologically.

Answer 5

• catecholaminergic system

- loss of substance in substantial nigra, and dorsal motor nucleus of vagus, and cortex

Question 6

Define the components of the motor system affected in amyotrophic lateral sclerosis and how their degeneration affects the patient’s function.

Answer 6

• motor cortex, anterior horn cells, some corticospinal tract and spinocerebellar tract involvement
• spasticity, weakness, difficulty walking, atrophy, fasciculations, increased reflexes, decreased strength

Question 7

Identify 3 common histological features of multiple sclerosis plaques, their most common anatomical localization and pattern of clinical course.

Answer 7

• well demarcated gray areas of demyelinization within the white matter, especially adjacent to ventricles
• patchy, random loss of myelin in optic nerves
• gliosis
• affects oligodenrocytes
• macrophages and T cells infiltrate around vessels
• anatomical sites: around ventricles, optic nerve

Question 8

What are the gross findings in Alzheimer diseased brain? How does it reflect clinical findings?

Answer 8

• narrowing of gyri of frontal lobe, also in parietal lobe and association cortices
• widening of sulci
• parietal: visual spatial problems
• loss of memory

Question 9

What is the anatomic basis of the cholinergic loss in Alzheimer disease?

Answer 9

Nucleus basalis of Meynert, which is rich in Ach, in anterior forebrain

Question 10

What are neurofibrillary tangles and how do they form?

Answer 10

-tau proteins are microtubule proteins which are released from the tubes and form aggregates in AD

Question 11

What are neuritic plaques? Where are they found?

Answer 11

• deposits of Abeta amyloid

- in grey matter

Question 12

What region of the CNS bear brunt of Huntington disease? How are these changes reflected clinically?

Answer 12

Basal Ganglia: caudate nucleus

• outer walls of ventricle flatten due to disappearing caudate
• clinically: depression, dementia, chorea

Question 13

What are diagnostic histologic features of Parkinson Disease?

Answer 13

-Lewy bodies inclusions: alpha-synuclein protein