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Amnesia Syndromes

Amnesia Syndromes. Lecture 21. Wernicke-Korsakoff’s Syndrome. Deficits similar to H.M. Anterograde retrograde more severe Cause: Long-term alcohol abuse Thiamine (vitamin B 1 ) deficiency required for glucose utilization Neurons die ~. Damage to Diencephalon. Hypothalamus

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Amnesia Syndromes

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  1. Amnesia Syndromes Lecture 21

  2. Wernicke-Korsakoff’s 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. Alzheimer’s 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 Alzheimer’s 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 • Down’s Syndrome also trisomy • Adults  Alzheimer’s ~

  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 Alzheimer’s • 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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