Neurodegenerative disorders

Question 1

What contaminent in illegal drugs can cause Parkinson’s -> toxicity of substantia nigra?

Answer 1

MPTP which is metabolised to MPP+

Question 2

What will be seen on histology / grossly in the brain in Parkinsons disease?

Answer 2

• Depigmentation of SN (loss of dopamenergic neurons)
• Lewy bodies: composed of alpha-synuclein (intracellular eosinophilic inclusions)

Question 3

What is the trinucletide repeat in Huntingtons disease?

Answer 3

CAG repeated in the Huntingtin (HTT) gene

Question 4

What chromsome is affected in Huntingtons?

Answer 4

Chromosome 4

Question 5

What are the symptoms of Huntington disease?

Answer 5

• Chorea
• Athetosis
• Aggression
• Depression
• Dementia

Question 6

What do neurons die via in Huntingtons?

Answer 6

NMDA-R binding and glutamate excitotoxicity

Question 7

What atrophies in Huntingtons?

Answer 7

Caudate and putamen

Question 8

What NTs are affected in Huntingtons?

Answer 8

• Increased dopamine
• Decreased GABA
• Decreased Ach

Question 9

What structures are atrophied in Huntingtons?

Answer 9

Caudate and putamen (dorsal striatum)

Question 10

Why are those with Downs syndrome at increased risk of Alzheimers?

Answer 10

APP is located on chr 21.
- APP synthesises Amyloid-Beta -> ALzheimers

Question 11

What NT is decreased in Alzheimers?

Answer 11

Ach

Question 12

What proteins are linked to increased risk of Alzheimers?

Answer 12

• ApoE-2 (decr risk of sporadic) and ApoE4 (decr risk of sporadic)
• APP, Presenilin-1, Presenilin-2

Question 13

What proteins are linked to familial early onset Alzheimers?

Answer 13

• APP
• Presenilin-1
• Presenilin-2

Question 14

What are the gross findings on the brain in Alzheimers?

Answer 14

• Widespread cortical atrophy
• Hippocampus atrophy
• Narrowing of gyri and widening of sulci

Question 15

What are the histological findings in Alzheimers?

Answer 15

• Senile plaques in gray mater: B amyloid core; may cause amyloid angiopathy
• Neurofibrillary tangles: intracellular, hyperphosphorylated tau protein = insoluble cytoskeletal elements
• Hirano bodies - intracellular eosinophilic proteinaceous rods in hippocampus

Question 16

What protein are Amyloid-B synthesised by?

Answer 16

APP

Question 17

How can Alzheimers cause intracranial hemorrhage?

Answer 17

Beta amyloid may cause amyloid angiopathy -> intracranial hemorrhage

Question 18

What are neurofibrillary tangles, where are they found/

Answer 18

Intracellular, hyperphosphorylated tau protein - insoluble cytoskeletal elements

Question 19

What will frontotemporal dementia present with?

Answer 19

Changes in personality/behaviour and aphasia

Question 20

What will be seen on histology in Frontotemporal dementia?

Answer 20

• Inclusions of hyperphosphorylated tau (round Pick bodies)
• Ubiquinated TDP-43

Question 21

What symptom can differentiate Lewy body dementia from others?

Answer 21

Visual halucinations

Question 22

Where are Lewy bodies found?

Answer 22

Intracellular in cortex

Question 23

What cvan be seen on imaging (MRI/CT) in vascular dementia?

Answer 23

Multiple cortical and/or subcortical infarcts

Question 24

What is 2nd most common cause of dementia in the elderly?

Answer 24

Vascular

Question 25

What are the major symptoms of Creutzfeld Jakob disease?

Answer 25

Rapidly progressive dementia with myoclonus and ataxia

Question 26

What will be seen on EEG in CJD?

Answer 26

Periodic sharp waves

Question 27

What will be found in CSF in CJD?

Answer 27

14-3-3 protein

Question 28

What will be seen in the cortex grossly in CJD?

Answer 28

Spongiform cortex (vacuuolation w/o inflammation)

Question 29

What happens to the prions in CJD?

Answer 29

the normal prion is transformed to a Beta-peated sheet resistant to proteases (PrPc -> PrPsc)

Question 30

HIV-associated dementia will lcause what grossly on the brain?

Answer 30

Diffuse gray matter and subcortical atrophy

Question 31

What will be seen histologically in HIV-associated dementia?

Answer 31

Microglial nodules with multinucleated giant cells

Question 32

What are the symptoms of HIV-associated dementia?

Answer 32

• Cognitive deficits
• Gait disturbances
• Irratibility
• Depressed mood