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 ~