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Amnesia%20Syndromes

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Amnesia Syndromes. Lecture 21. Wernicke-Korsakoff's Syndrome. Deficits similar to H.M. ... Down's Syndrome also trisomy. Adults Alzheimer's ~ Cholinergic Degeneration ... – PowerPoint PPT presentation

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Title: Amnesia%20Syndromes


1
Amnesia Syndromes
  • Lecture 21

2
Wernicke-Korsakoffs Syndrome
  • Deficits similar to H.M.
  • Anterograde
  • retrograde more severe
  • Cause Long-term alcohol abuse
  • Thiamine (vitamin B1 ) deficiency
  • required for glucose utilization
  • Neurons die

3
Damage to Diencephalon
  • Hypothalamus
  • Mammilary bodies
  • mammilothalamic tract
  • Thalamus
  • reciprocal inputs w/ prefrontal cortex
  • temporal sequence

4
Alzheimers Disease
  • Profound memory loss
  • 1/4 of all 85-yr-olds
  • Effects on memory
  • Procedural O.K.
  • Declarative deficits
  • Personality changes
  • Diagnosis only certain at autopsy
  • Widespread brain atrophy
  • plaques and tangles

5
Neurofibril Tangles
  • Inside neuron
  • Forebrain cortex
  • Tau proteins
  • toxic
  • abnormal

6
Amyloid Plaques
  • Extracellular
  • Beta amyloid protein
  • From degenerating neurons
  • Found in everyone
  • More abundant in Alzheimers patients

7
Alternate Enzymatic Splicing?
  • Beta amyloid precursor protein
  • BAPP
  • Cleaved by enzyme
  • normal protein
  • beta amyloid

8
Alternate splicing model BAPP
Protease regulating region
amyloid Beta region
9
Alternate splicing model BAPP
Normal splicing
10
Alternate splicing model BAPP
Alternative splicing
11
Alternate splicing model BAPP
Alternative splicing
Beta amyloid
12
Causes Genetic Model
  • Very old
  • mild nonfamilial form
  • Chromosome 21 trisomy
  • BAPP gene encoding amyloid
  • Apolipoprotein E - APOE
  • Gene variant onset age correlated
  • Downs Syndrome also trisomy
  • Adults ? Alzheimers

13
Cholinergic Degeneration
  • Decreased Cholinergic activity
  • Postsynaptic receptors populations OK
  • Ach-releasing neurons die off

14
Treatment?
  • Choline?
  • not effective
  • ACh agonists?
  • AChE inhibitors
  • Tacrine
  • effective in 33
  • Stem cells?

15
Chronic Inflammation Model
  • Anti-inflammatory (NSAID)
  • slowed progression
  • Arthritic patients treated with NSAIDs
  • less likely to have Alzheimers
  • Microglia
  • Phagocytosis
  • Overactive inflammatory response?

16
Recent Developments
  • Role of beta amyloid Tau
  • cause or effect?
  • Abnormal beta amyloid is causal
  • successfully blocked
  • triggers changes in Tau
  • Tau
  • neurofibrillary tangles are toxic
  • Beta amyloid detected in CSF
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