Path Notes

Question 1

What is the key to pathogenesis of CNS Dementia and neurodegenerative disorders?

Answer 1

Abnormal protein homeostasis

Question 2

Gender difference in Alzheimer’s

Answer 2

Women slightly more likely

-odds for any one woman now exceeds breast cancer

Question 3

Where do amyloid plaques tend to be more numerous?

Answer 3

Deep cortical layers

Question 4

What are filamentous intracellular inclusions made of? What are they called?

Answer 4

• Tau protein
• Neurfibrillary tangles (NFTs)
• Neuropil thrads (NTs)

Question 5

What part of the brain does plaques and tangles spare?

Answer 5

Occipital lobe, primary motor cortex

Question 6

Where can plaques and tangles be found early on in Alzheimers?

Answer 6

Hippocampus

Question 7

What are the 2 AB peptides?

Answer 7

AB 40 = bad

AB 42 = worse, seed

Question 8

What is amyloid angiopathy?

Answer 8

AB deposits in cortical and leptomeningeal arteries and arterioles

Question 9

What are Hirano bodies?

Answer 9

Intracellular aggregates of actin and actin-associated proteins

Question 10

Where are Hirano bodies frequently found?

Answer 10

Hippocampal pyramidal cells

Question 11

What is Tau?

Answer 11

microtubule associated protein

Question 12

What happens to Tau in Alzheimer’s?

Answer 12

• Hyperphosphorylated

- Lose ability to bind to microtubules

Question 13

What ApoE alleles have higher/lower risk for AD?

Answer 13

E4 = higher risk
E2 = lower risk

Question 14

What 3 Genes are associated with early onset AD

Answer 14

• APP
• Presenilin 1
• Presenilin 2

All autosomal dominant

Question 15

3 Types of Frontotemporal Lobar Degeneration (FTLD):

Answer 15

• Tau
• TDP
• FUS

Question 16

Knife-edge gross examination of brain suggests:

Answer 16

Tau form of Frontotemporal Lobar Degeneration (FTLD)

Question 17

Which type of FTLD is related to ALS?

Answer 17

FTLD-TDP

Question 18

Which type of FTLD is most common?

Answer 18

Tau type

Question 19

3 Hallmark symptoms of Parkinson’s:

Answer 19

Tremor
bradykinesia
Rigidity

Question 20

What are Lewy Bodies made of?

Answer 20

Alpha-synuclein

Question 21

Difference of Progressive Supranuclear Palsy vs. Parkinson’s

Answer 21

No Lewy Bodies in PSP

Question 22

Important exam finding in PSP:

Answer 22

Difficulty with voluntary eye movements

Question 23

Histological findings in PSP:

Answer 23

• Globose tangle

- Tufted astrocyte

Question 24

Exam and histological findings in Corticobasal Degernation (CBD)

Answer 24

Exam: jerking of limbs, dyspraxia (cognitive dysfunction)

Histology: Ballooned neuron

Question 25

When does trinucleotide repeat expansion occur in Huntingtons?

Answer 25

Spermatogenesis

Question 26

Where does atrophy occur in Huntington’s?

Answer 26

Caudate and Striate

Question 27

Freidreich’s ataxia age of onset:

Answer 27

1st or 2nd decade of life

Question 28

Disease associated with Freidreich’s Ataxia:

Answer 28

Diabetes (1/4 of patients)

Question 29

Genetics of Freidreich’s Ataxia:

Answer 29

• GAA trinucleotide repeat on 9q13 frataxin protein

- Autosomal recessive

Question 30

Exam finding of ALS:

Answer 30

• Foot drop
• Muscle cramps
• Sensation preserved

Question 31

Proteins associated with Spinal Muscular Atrophy

Answer 31

• SMN1, SMN2

- Gene needed for motor neuron survival

Question 32

Diseases with Tau:

Answer 32

• Alzheimer’s
• FTLD
• Parkinson’s
• PSP
• CBD