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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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wernicke korsakoff s syndrome
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 ~
damage to diencephalon
Damage to Diencephalon
  • Hypothalamus
    • Mammilary bodies
    • mammilothalamic tract
  • Thalamus
    • reciprocal inputs w/ prefrontal cortex
    • temporal sequence ~
alzheimer s disease
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 ~
neurofibril tangles
Neurofibril Tangles
  • Inside neuron
    • Forebrain & cortex
  • Tau proteins
    • toxic
    • abnormal ~
amyloid plaques
Amyloid Plaques
  • Extracellular
  • Beta amyloid protein
    • From degenerating neurons
  • Found in everyone
    • More abundant in Alzheimer’s patients ~
alternate enzymatic splicing
Alternate Enzymatic Splicing?
  • Beta amyloid precursor protein
    • BAPP
  • Cleaved by enzyme
    • normal protein
    • beta amyloid ~
slide8

Alternate splicing model: BAPP

Protease regulating

region

amyloid

Beta region

slide10

Alternate splicing model: BAPP

Alternative splicing

slide11

Alternate splicing model: BAPP

Alternative splicing

Beta amyloid

causes genetic model
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 ~
cholinergic degeneration
Cholinergic Degeneration
  • Decreased Cholinergic activity
    • Postsynaptic receptors populations OK
    • Ach-releasing neurons die off ~
treatment
Treatment?
  • Choline?
    • not effective
  • ACh agonists?
    • AChE inhibitors
    • Tacrine
    • effective in 33%
  • Stem cells?
chronic inflammation model
Chronic Inflammation Model
    • Anti-inflammatory (NSAID)
    • slowed progression
  • Arthritic patients treated with NSAIDs
    • less likely to have Alzheimer’s
  • Microglia
    • Phagocytosis
    • Overactive inflammatory response? ~
recent developments
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 ~