24. Neuropathology of Degenerative Diseases

Question 1

Alzheimer’s: location where it primarily presents in the brain? types of proteins involved?

Answer 1

cortical.
neurofibrillary tangles (tau) and senile plaques (beta-amyloid)

Question 2

Huntington’s: location where it primarily affects the brain and types of proteins involved?

Answer 2

caudate/extrapyramidal motor system. Trinucleotide repeat disease. (proteins with abnormally expanded poly-glutamine repeats)

Question 3

what is the extrapyramidal system?

Answer 3

part of the motor system, causes involuntary reflexes and movement, and modulation of movement (ie coordination). modulates/indirect control of anterior horn cells.
modulate motor activity without directly innervating motor neurons.

Question 4

what is the pyramidal system? which pathways?

Answer 4

corticospinal and some corticobulbar tracts, directly innervate motor neurons of the spinal cord or brainstem.

Question 5

Parkinson’s: location where it primarily affects the brain? types of proteins involved?

Answer 5

Substantia nigra pars compacta

synuclein

Question 6

Huntingtons and Parkinson’s can both progress from a motor disturbance to what?

Answer 6

both can eventually include dementia.

Question 7

Amylotrophic Lateral Sclerosis (ALS) location in brain, proteins involved?

Answer 7

motor system (degeneration of both lower and upper)
selective degeneration of ventral roots
atrophy of grouped fiber types seen on biopsy (patchwork)

Question 8

Alzheimer’s is found with inc incidence around what age?

Answer 8

beginning at age 60

Question 9

Alz: how do patients present?

Answer 9

memory loss (esp for memory of recent events), loss of initiave, difficulty in word finding and calculation, disorientation to time and place.

Question 10

Alz: diagnosis?

Answer 10

no diag test: diagnostic efforts aimed ar ruling out other, treatable causes. Diag of exclusion

Question 11

what are some reversible causes of dementia?

Answer 11

• metabolic disturbances
• infection (UTI, pneumonia)
• psychiatric (depression can present as Alz in the elderly)

Question 12

Alz: appearance on gross pathology?

Answer 12

pan-lobar cortical atrophy (entire brain, with some sparing of the occipital lobes)

Question 13

Alz: appearance of gross path on coronal section?

Answer 13

dilation of ventricles as a consequence of loss of brain parenchyma (hydrocephalus ex vacuo)

Question 14

Alz: histology?

Answer 14

flame-shaped neurofibrillary tangle (tau)
spoltch-shaped plaque of beta-amyloid
These are both present in non-Alz brains, but are present in greater numbers with Alz. No cutoff number has been established.

Question 15

Alz: loss of recent memory on presentation can progress to what?

Answer 15

personality problems that we associate with frontal lobe damage

Question 16

Is biopsy used for dx of Alz?

Answer 16

would only be done to rule out something else. requires a big amount of tissue from the hippocampus, not generally done.

Question 17

Alz: what is the deal with ApoE4?

Answer 17

part of the processing pathway of the Amyloid Precursor Protein: ApoE is involved in removing the gamma-secretase product from the brain: ApoE4 version of ApoE makes removal slower –> buildup and neurotoxicity

Question 18

General: treatment for Alz?

Answer 18

acetylcholine esterase inhibitor (donepazil)

NMDA receptor antagonist (memantine)

Question 19

what are the 2 versions of Tau to be concerned about?

Answer 19

Tau with 3-repeat and Tau with 4-repeat. some diseases have more of one type or the other, can be helpful in diagnosis?

Question 20

Pick’s disease: gross brain appearance?

Answer 20

profound frontotemporal corctical atrophy. less extensive than Alz (no parietal, less temporal lobe involvement)
(The disease PICKs the front of the brain)

Question 21

Pick’s disease histology: what do pick cells look like?

Answer 21

large swollen neurons in the affected cortex. balloon cytoplasm. full of Tau protein

Question 22

Parkinson’s disease should respond to what medication?

Answer 22

Sinemet: (combination of carbidopa and levodopa)

Question 23

Park: clinical triad?

Answer 23

tremor, bradykinesia, rigidity

better to remember TRAP: tremor, rigidity, ataxia/bradykinesia, postural instability

Question 24

Park: pt appearance at onset?

Answer 24

acryonym: TRAP (tremor, rigidity, akinesia, postural instability)
unilateral tremor, less movement, stiffness. pill rolling tremor at REST, shuffling posture, loss of affect in face.

Question 25

what is meant by rigidity in Park?

Answer 25

difficulty initiating movement, cog-wheeling (initial resistance, then sudden give)

Question 26

Park: degeneration where?

Answer 26

degen of substantial nigra (loss of pigment) and locus ceruleus

Question 27

Park: classic histo finding?

Answer 27

Lewy bodies (nearly round very pink cytoplasmic inclusion). accumulation of synuclein.

Question 28

how can we distinguish between parkinson’s disease and another disease with parkinsonism as a feature?

Answer 28

response to Sinemet (carbidopa/levodopa)

Question 29

ALS: classic presentation?

Answer 29

wasting due to lower motor neuron involvement, and hyper-reflexia in lower extremities due to upper motor neuron involvement

Question 30

Huntington’s: age of onset?

Answer 30

30-50

Question 31

Huntingtons: clinical manifestations?

Answer 31

• chorea (excessive, uncontrolled movement)
• dementia
• can begin with abnormalities of subtle movement (fidgeting) or mentation (personality change)

Question 32

Huntington’s: gross/coronal appearance?

Answer 32

huge ventricles due to atrophy of caudate and cortical loss.