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28 Cards in this Set

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What mutations are associated with Alzheimer's disease?
In what chromosomes can they be found?
PS2 - chromosome 1
PS1 - chromosome 14
APP - chromosome 21; - most important. Also associated with Down's syndrome.
What are the 3 main histological findings in Alzheimer's disease?
1. Neuritic plaques - around neurones
2. Neurofibrillary tangles - intracellular bundles of filament in the cytoplasm
3. Amyloid angiopathy - perivascular deposit of amyloid (plaques)
What parts of the brain are mostly affected by Alzheimer's disease?
Hippocampus, amygdala.
What other processes you might observe in Alzheimer's disease?
- Hirano bodies: elongated glassy eosinophilic, crystalline beaded bodies.
- Granulovacuolar degeneration of neurons.
What are the hallmark clinical features of Parkinson's disease?
TRAP

Tremor
Rigidity
Akinesia/Bradykinesia
Postural instability
What is the main component of:
- Plaques
- Tangles
Plaques:
beta amyloid oligomers in centre and dystrophic nerve terminals with hyperphosphorylated tau around it.

Tangle - intracellular:
Hyperphosphorylated tau leading to neurofilaments destabilising and form tangles.
Describe the process of beta amyloid formation.
Amyloid Precursor Protein (APP) on the cell membrane might be processed by either alpha or beta secretase, which later broken down by gamma secretase. This process occurs extracellularly.

Alpha secretase pathway - p3
Beta secretase pathway - beta amyloid (A beta); 40 or 42 A beta.
What are the 3 parts of APP (Amyloid Precursor Protein) and what are their functions?
1. Head - activates apoptotic system
2. A beta - maintains synapses. Binds to Ach receptor.
3. Tail (AICD) - calcium homeostasis.
What are the characteristics of neurons in Alzheimer's disease?
- ↓ number of synapses
- ↓ number of cells
- ↓ AMPA type
- ↓ spine density (spines - sites of excitatory synapses)
- NMDA receptor unaffected
Presenilin is a part of gamma secretase. What are its functions?
- Catalyse formation of A beta
- Modulate release of Ca2+ from sarcoplasmic reticulum to cytoplasm.
- regulating Ca2+ store release to presynaptic.
What are the current accepted therapeutic approaches for Alzheimer's disease?
For worsen progress:

Anticholinesterase

Cholinomimetics

Glutamate (NMDA) receptor antagonists
What are the histology features of Parkinson disease?
- Loss of pigmented cathecolamine neurons.
- Lewy bodies in the remaining neurons.
- Neuromelanin pigment intracellularly
What are the pathology features of Huntington's disease?
- Atrophy of caudate and putamen
- Widespread cerebral atrophy - striatum, cerebral cortex.
Where can you find the major language input area? Major output area?
Language input - Wernicke's area.
Brodman's area 22, temporal lobe.

Language output - Broca's area.
Brodman's area 44, 45; Frontal lobe.
What is the major connection between language input and output area?
- Arcuate fasciculus
- Peri-sylvian fissure
What are the 3 language skills tested clinically?
1. Repetition - arcuate fasciculus
2. Comprehension - Wernicke's to other cognitive areas
3. Expression - Other cognitive areas to Broca's
What is Wernicke's aphasia?
Loss of comprehension plus word meaning
What is Broca's aphasia?
Loss of expression plus grammar
What is conductive aphasia (arcuate fasciculus)?
Loss of repetition.
What is transcortical sensory aphasia?
Loss of comprehension but reserved repetition.
What is transcortical motor aphasia?
Loss of expression but preserved repetition.
How do you classify aphasia?
.
What is anosognosia?
What aphasia is associated with this?
Unawareness of deficit.
Associated with Wernicke's aphasia.
What is the vascular supply of the motor areas?
Broca's - MCA superior division territory
Wernicke's - MCA inferior division territory.
What is the result of:
- MCA - ACA watershed infarct
- MCA - PCA watershed infarct
MCA-ACA: Broca's area is isolated - motor transcortical aphasia

MCA-PCA: Wernicke's area is isolated - sensory transcortical aphasia
What is the associated neurological deficit with:
Broca's aphasia?
Weakness of the right face and right arm and dysarthria are common - due to close location with the motor homunculus.
What is the associated neurological deficit with:
Wernicke's aphasia?
Mild or absent of contralateral visual field, especially affecting the right upper quadrant - due to close association with visual cortex.
Do you have writing impairment with aphasia normally?
Yes, disturbance of language seen with spoken input and output is also seen with written input and output.