1. Amnesia Syndromes Lesson 22

2. Wernicke-Korsakoff’s Syndrome n Deficits similar to H.M. l Anterograde l retrograde more severe n Cause: Long-term alcohol abuse n Thiamine (vitamin B 1 ) deficiency l required for glucose utilization l Neurons die ~

3. Damage to Diencephalon n Hypothalamus l Mammilary bodies l mammilothalamic tract n Thalamus l reciprocal inputs w/ prefrontal cortex l temporal sequence ~

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

5. Neurofibril Tangles n Inside neuron l Forebrain & cortex n Tau proteins l toxic l abnormal ~

6. Amyloid Plaques n Extracellular n Beta amyloid protein l From degenerating neurons n Found in everyone l More abundant in Alzheimer’s patients ~

7. Alternate Enzymatic Splicing? n Beta amyloid precursor protein l BAPP n Cleaved by enzyme l normal protein l beta amyloid ~

8. Alternate splicing model: BAPP amyloid Beta region Protease regulating 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 n Very old l mild nonfamilial form n Chromosome 21 trisomy l BAPP gene encoding amyloid l Apolipoprotein E - APOE l Gene variant & onset age correlated n Down’s Syndrome also trisomy l Adults  Alzheimer’s ~

13. Cholinergic Degeneration n Decreased Cholinergic activity l Postsynaptic receptors populations OK l Ach-releasing neurons die off ~

14. Treatment? n Choline? l not effective n ACh agonists? l AChE inhibitors l Tacrine l effective in 33% n Stem cells?

15. Chronic Inflammation Model n Anti-inflammatory (NSAID) l slowed progression n Arthritic patients treated with NSAIDs l less likely to have Alzheimer’s n Microglia l Phagocytosis l Overactive inflammatory response? ~

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