6.4.2 Neurodegenerative Diseases

Question 1

What is the white arrow pointing at?

Answer 1

Lewy body in substania nigra

Question 2

What is the main type of deposit in FTLDs?

Answer 2

Tau deposits

Question 3

Prior to death, this patient demonstrated signs of dementia. What is the most likely cause of this patient’s dementia?

Answer 3

DLB (not Alz Dz because there is no cortical atrophy)

DLB often has a normal brain weight with little to no atrophy

Question 4

What is the most common genetic cause of ALS?

Answer 4

C9orf72- intronic hexanucleotide expansion (open frame mutation)

Question 5

What is the most common neurodegenerative dz behind Alz Dz?

Answer 5

Dementia with Lewy bodies (DLB)

Question 6

What are the two primary protein aggregates in AD?

Answer 6

Beta-amyloid plaques (extracellular)

Phosphorylated tau tangles and threads (intracellular)

Question 7

What are major degenerative disorders that cause adult dementia?

Answer 7

Alzheimer disease, Dementia with Lewy bodies, Frontotemporal lobar dementia (Pick dz)

Question 9

What are the main clinical features of a patient with Parkinson dz?

Answer 9

resting tremor, bradykinesia (or akinesia), rigidity that may be initially unilateral but progressees to involve both sides

Question 10

Which lobes of the brain are primarily affected by AD? Which lobe of the brain is typically preserved?

Answer 10

Atrophy prominent in temporal pole, medial temporal lobe (amygdala and hippocampus), frontal and partietal lobes

Preserved: Occipital lobe

Question 11

What type of proteinopathy are these conditions?

Answer 11

Question 12

What is the common thread between protein aggregates that lead to disease?

Answer 12

The native protein structure is lost, and fibrils form and accumulate

Question 13

What are some genes that have been linked to Alz Dz?

Answer 13

APP, PS1, PS2, ApoE4

Question 14

What are some of the genetic loci that have been identified in AD or AR inherited Parkinson dz?

Answer 14

LRRK2, gene for alpha-synuclein

Question 15

Name this condition. What is the importance of fluorescence on Thioflavin S staining?

Answer 15

AD; Fluorescence confirms beta-pleated sheet conformation of protein aggregate

Question 16

What is the black arrow pointing at? What protein comprises that aggregate?

Answer 16

Lewy body; alpha-synuclein

In DLB: Lewy bodies accumulate in brain stem, pons, limbic areas, neocortex

Question 17

Which protein aggregate found in AD correlates better with dementia?

Answer 17

Tau “tangles” (ptau)

Question 18

Diagnose him

Answer 18

Parkinson Dz

Question 19

What intracellular inclusion is being stained in these slides?

Answer 19

Tau neurofibrillary tangles

Question 20

Name this condition

Answer 20

Pick dz (FTLD-tau)

Question 21

What is the neuropathology and the affected areas of ALS?

Answer 21

Question 22

How can Parkinson Dz be distinguished from other extrapyramidal movement disorders at autopsy?

Answer 22

Presence of lewy bodies in the surviving neurons of the brainstem

Question 23

What disease? What is shown in these images?

Answer 23

Parkinson dz

1st 2 images: substantia nigra compacta cell loss, loss of striatal dopamine content

3rd image: Lewy body

Question 24

What are the main clinical features of frontal temporal lobar degeneration (FTLD)?

Answer 24

Progressive language deterioration and personality changes

Question 25

Describe these conditions [ALS, Alz dz, Parkinson dz, dementia with lewy bodies (DLB), FTLD (pick dz)] as either cerebral cortical disorders or motor pathway disorders.

Answer 25

Question 26

Answer 26

Pick bodies and Pick cells Severe neuronal loss in outer cortical layers Pick cells are swollen pale neurons (ballooned neurons)

Question 27

Name two alpha-synucleinopathies.

Answer 27

Dementia with lewy bodies (dementia Parkinson Dz (movement disorder)

Question 28

What are the clinical features of DLB?

Answer 28

Progressive dementia with flucuations in coginition and arrousal REM sleep behavior disorder Visual halLEWYnations Variable mild parkinsonism

Question 29

Answer 29

Question 30

What pathologic feature of AD are the red arrows pointing at? Why does this occur?

Answer 30

Hydrocephalus ex vacuo: occurs in response to atrophy of the cerebral lobes, not as a result of excessive CSF production

Question 31

Name the type of dz

Answer 31

FTLD

Question 32

What type of protein is tau\>

Answer 32

Axonal microtubule-associated protein (MAP)

Question 33

Name this condition

Answer 33

Alzheimer Disease

Question 34

What type of aggregates can be found in motor neurons of ALS patients?

Answer 34

TDP-43

Question 35

What gene is associated with Alzheimer disease because of its role in processing of amyloid precursor proteins? Chromosome?

Answer 35

APP gene on chromosome 21

Question 36

What neurotransmitter is decreased in the cortex of a patient with AD?

Answer 36

Ach