Neurodegenerative disorders Flashcards
What contaminent in illegal drugs can cause Parkinson’s -> toxicity of substantia nigra?
MPTP which is metabolised to MPP+
What will be seen on histology / grossly in the brain in Parkinsons disease?
- Depigmentation of SN (loss of dopamenergic neurons)
- Lewy bodies: composed of alpha-synuclein (intracellular eosinophilic inclusions)
What is the trinucletide repeat in Huntingtons disease?
CAG repeated in the Huntingtin (HTT) gene
What chromsome is affected in Huntingtons?
Chromosome 4
What are the symptoms of Huntington disease?
- Chorea
- Athetosis
- Aggression
- Depression
- Dementia
What do neurons die via in Huntingtons?
NMDA-R binding and glutamate excitotoxicity
What atrophies in Huntingtons?
Caudate and putamen
What NTs are affected in Huntingtons?
- Increased dopamine
- Decreased GABA
- Decreased Ach
What structures are atrophied in Huntingtons?
Caudate and putamen (dorsal striatum)
Why are those with Downs syndrome at increased risk of Alzheimers?
APP is located on chr 21.
- APP synthesises Amyloid-Beta -> ALzheimers
What NT is decreased in Alzheimers?
Ach
What proteins are linked to increased risk of Alzheimers?
- ApoE-2 (decr risk of sporadic) and ApoE4 (decr risk of sporadic)
- APP, Presenilin-1, Presenilin-2
What proteins are linked to familial early onset Alzheimers?
- APP
- Presenilin-1
- Presenilin-2
What are the gross findings on the brain in Alzheimers?
- Widespread cortical atrophy
- Hippocampus atrophy
- Narrowing of gyri and widening of sulci
What are the histological findings in Alzheimers?
- 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
What protein are Amyloid-B synthesised by?
APP
How can Alzheimers cause intracranial hemorrhage?
Beta amyloid may cause amyloid angiopathy -> intracranial hemorrhage
What are neurofibrillary tangles, where are they found/
Intracellular, hyperphosphorylated tau protein - insoluble cytoskeletal elements
What will frontotemporal dementia present with?
Changes in personality/behaviour and aphasia
What will be seen on histology in Frontotemporal dementia?
- Inclusions of hyperphosphorylated tau (round Pick bodies)
- Ubiquinated TDP-43
What symptom can differentiate Lewy body dementia from others?
Visual halucinations
Where are Lewy bodies found?
Intracellular in cortex
What cvan be seen on imaging (MRI/CT) in vascular dementia?
Multiple cortical and/or subcortical infarcts
What is 2nd most common cause of dementia in the elderly?
Vascular
What are the major symptoms of Creutzfeld Jakob disease?
Rapidly progressive dementia with myoclonus and ataxia
What will be seen on EEG in CJD?
Periodic sharp waves
What will be found in CSF in CJD?
14-3-3 protein
What will be seen in the cortex grossly in CJD?
Spongiform cortex (vacuuolation w/o inflammation)
What happens to the prions in CJD?
the normal prion is transformed to a Beta-peated sheet resistant to proteases (PrPc -> PrPsc)
HIV-associated dementia will lcause what grossly on the brain?
Diffuse gray matter and subcortical atrophy
What will be seen histologically in HIV-associated dementia?
Microglial nodules with multinucleated giant cells
What are the symptoms of HIV-associated dementia?
- Cognitive deficits
- Gait disturbances
- Irratibility
- Depressed mood
