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
