by mtoom


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How does DSM-IV define dementia?
  • Gradual, progressive, permanent loss of intellectual faculties
  • Memory impairment and at least one of the following: aphasia, apraxia, agnosia or executive dysfunction
  • Interferes with social or occupational function
What is by far the most common cause of dementia? *
Primary neurodegenerative disease
Most cases of dementia are which disease?
  • What are 2 other major causes? 
#1 Alzheimer's disease

Also:
  • Vascular disease
  • Parkinson's
What is meant by mixed dementia?
In reality, many cases of dementia do not clearly fit into a firm diagnosis like AD or Parkinson's
What are the 3 key pathological findings in Alzheimer's disease?
  • Senile plaques
  • Neurofibrillary tangles
  • Dystrophic neurites
What are 2 major gross pathological findings in Alzheimer's disease?
  • Atrophy of cerebrum
  • Shrinkage of gyri
  • Ventricles larger
Senile plaques
  • Are made of what?
  • Where are they found?
  • Beta-amyloid (Aβ protein)
  • Found in extracellular space
Neurofibrillary tangles
  • Are made of what?
  • Where are they found?
  • Tau protein
  • Within neuron
Dystrophic neurites
  • What are they?
  • What are these made up of?
  • Projections of neurons
  • They are made up of Tau among other things
In terms of the brain's lobes, where are the senile plaques and neurofibrillary tangles found in Alzheimer's?
  • Laterally in the temporal lobe
  • Medially in the limbic lobe (and hippocampus)
Aβ-protein has varying size (from 39 to 43 amino acids)
  • What can be said about the larger size Aβ-protein?
More amyloidogenic and neurotoxic
The Aβ-protein is part of what protein?
  • What is its purpose?
It is part of the APP (amyloid precursor protein)
  • Purpose is to anchor APP to the cell membrane 
Describe what APP-secretase α and APP-secretase β do?
  • What is the difference? 
α and γ cut the APP protein such that an amyloidogenic precursor is not generated

β and γ cut the APP protein such that an amyloidogenic precursor is generated (i.e. Aβ protein)
What kind of familial AD are these in terms of onset and inheritance?
  • APP gene 
  • PS-1
  • PS-2
Early-onset
  • Dominant inheritance 
What kind of familial AD are these in terms of onset and inheritance?
  • ApoE 
Late-onset
  • Inheritance higher than by chance by not dominant 
APP mutations near the enzymatic cleavage site are likely to result in what?
Increased production of Aβ protein
PS-1 and PS-2 are part of what?
γ-secretase
What does ApoE isoform E4 mean in terms of amyloidogenic risk?
Higher risk

Homozygous > heterozygous > no copies
How does ApoE isoform E4 contribute to increased development of amyloid plaques?
Increases sequesting of Aβ protein, allowing it to aggregate into amyloid
Why do people with Down's syndrome get Alzheimer's disease?
They have an extra copy of chromosome 21 where APP gene resides
  • More conversion of APP gene to APP protein 
How does head trauma increase Alzheimer's risk?
Increases conversion of APP gene to APP protein
How do APP, PS1 and PS2 mutations increase Alzheimer's risk?
Increase conversion of APP to Aβ protein
Does APO E4 increase Alzheimer's risk?
Increases rate at which Aβ protein is converted to amyloid by sequesting Aβ protein
Do non-demented people get plaques too?
Yes, about 80% of people who die in their 80s will have such plaques
Neurofibrillary tangles
  • Made up of what protein?
  • Form what ultrastructure
  • Made up of Tau protein
  • Form paired helical filaments
What causes Tau to form paired helical filaments?
Phosphorylation
Paired helical filaments made of Tau protein are major components of what? (2)
  • Neurofibrillary tangles
  • Plaque-associated neurites
Do neurofibrillary tangles occur in any conditions other than Alzheimers?
Yes, dozens... They are not unique to Alzheimer's
What role does inflammation play in Alzheimer's?
  • What cell type does it come from?
  • What drugs help with the inflammation?
Chronic, low grade inflammation
  • Microglia
  • Anti-inflammatories
Inflammation contributes to what parts of the development of amyloid?
All of them
The neurotransmitters in Alzheimer's disease come from where?
  • Which neurotransmitter is involved? 
Nucleus basilis
  • ACh
What happens to ACh levels in Alzheimer's disease?
Reduced

(that's why drugs that increase ACh help Alzheimer's disease, e.g. cholinesterase inhibitor)
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