Lecture 23: CNS Pathology

Question 1

Common feature of all neurodegenerative diseases

Answer 1

Insoluble protein aggregates build up and lead to neurotoxic effects -> brain atrophy

Question 2

Alzheimer’s

Answer 2

• Amyloid Precursor Protein (APP) gene assoc.; affects age of onset
  Pathological diagnosis:
• Brain atrophy
• Tau NFTs
• Beta-amyloid neuritic plaques
• Spreads from bottom to top

Question 3

Alzheimer’s scoring

Answer 3

ABCs
A: (amyloid) Thal phasing; deposition extent top -> down
B: Braak staging; tau NFT extent bottom -> top
C: CERAD score; plaque freq.

Question 4

Protein aggregate ID

Answer 4

Tau NFTs (IHC) (AD)

Question 5

Protein aggregate ID

Answer 5

Tau NFTs (silver stain) (AD)

Question 6

Protein aggregate ID

Answer 6

Amyloid neuritic plaques; notice core w/ halo (AD)

Question 7

Frontotemporal Lobar Disease (FTLD)

Answer 7

1. Behavioral variant (60%)
2. Primary Progressive Aphasia (PPA, 40%)
   - TDP-43 protein involved; assoc. w/ progranulin Mx

Question 8

Protein aggregate ID

Answer 8

TDP-43 inclusions (FTLD)

Question 9

Pick Disease

Answer 9

Rare FTLD variant
- Unique w/ Pick bodies (silver or tau stain)

Question 10

Protein aggregate ID

Answer 10

Pick bodies (Pick FTLD)

Question 11

Protein aggregate ID

Answer 11

Tau immunostain for Pick bodies (Pick FTLD)

Question 12

Protein aggregate ID

Answer 12

Silver stain for Pick bodies (Pick FTLD)

Question 13

Amylotrophic Lateral Sclerosis (ALS)

Answer 13

• Upper + lower motor neuron degen.
• Early/middle age onset, rapid course
• Precentral gyrus shrinkage
• Variable inclusions; ubiquitin, TDP-43, FUS, etc.
• Lower motor: symmetric atrophy, fasciculation
• Upper motor: hyperreflexia, spasticity

Question 14

Protein aggregate ID

Answer 14

Bunina bodies, assoc. w/ ALS

Question 15

Protein aggregate ID

Answer 15

Ubiquitin immunoreactive neuronal inclusions (ALS)

Question 16

Protein aggregate ID

Answer 16

FUS stain (ALS)

Question 17

Parkinson’s

Answer 17

Clinical disease; core features:
- Hypo/bradykinesia
- Resting tremor
- Postural instability
- Rigidity
Non-idiopathic Parkinsoniasm causes can be: flu, trauma, drugs/toxins, multiple sys. atrophy, familial

Pathology:
- Depigment. of substantia nigra, locus ceruleus (loss of neural melanin from dopaminergic neuron death)
- Lewy bodies (alpha-synuclein) inclusions

Assoc. w/ PARK1/2, PARK3-11 genes

Question 18

Protein aggregate ID

Answer 18

Lewy bodies (alpha synuclein) (Parkinson’s)

Question 19

Dementia w/ Lewy Bodies (DLB)

Answer 19

• Freq. presents w/ AD; 2nd most common dementia
• Clinical/path. continuum w/ Parkinson’s
• More loss in limbic sys., less in cortex vs. AD
• Lewy bodies also found in neuronal processes; Lewy neurites
• Cognitive decline, hallucinations*, spont. Parkinsoniasms

Question 20

Huntington’s

Answer 20

• Familial autosomal dom. CAG trinucleotide repeats
• More repeats -> earlier onset
• Striatum (caudate, putamen) + frontal cortex degen./gliosis
• Spasms, progressive deterioration

Question 21

Protein aggregate ID

Answer 21

Lewy neurites in hippocampus (DLB)

Question 22

Protein aggregate ID

Answer 22

Lewy bodies

Question 23

Protein aggregate ID

Answer 23

Lewy bodies

Question 24

Creutzfeldt-Jakob Disease (CJD)

Answer 24

Prion disease w/ PrP protein aggregates
- Prion diseases can be sporadic, transmissible, or inherited

Question 25

Pathological ID

Answer 25

Spongiform changes w/ occasional joined larger cyst-like spaces assoc. w/ CJD

Question 26

Types of sports related head trauma

Answer 26

Concussive and non-concussive - Non-concussive over time drives disease - Brain axonal/vessel injuries over time accumulate -> CTE

Question 27

Chronic Traumatic Encephalopathy (CTE)

Answer 27

- Progressive neurodegen. w/ repetitive head trauma - Behavioral, cognitive symptoms Hyperphosphorylated tau pathology (p-tau): - Perivascular accumul. at cortical sulcus - Top-down patchy spread

Question 28

Protein aggregate ID

Answer 28

Perivascular P-tau patches at depth of sulci; CTE

Question 29

Tau NFTs

Answer 29

Bundles of paired helical p-tau filaments in neuronal cytoplasm, surround nucleus

Question 30

MAPT gene

Answer 30

Mx assoc. w/ inherited FTLD-tau