notes AD

  1. coronal
    front (ventral) and back (dorsal)
  2. where are high concentration so amyloid found?
    • amygdala
    • hippocampus
  3. white matter infarcts
    losing blood flow, lack of oxygen
  4. what are risk factors for AD
    • genetics and aging
    • history of depression
    • infarcts
    • head injury
  5. shuffling gait
    imbalance of NT (inability of brain to give subtle commands)
  6. homeopathic medicine
    body can heal itself, illnesses as body's attempt at regaining health
  7. APPswe
    increase BACE1 cleavage and increase in Ab peptides
  8. what kind of mutations are normally seen in PS1
    single amino acid missense mutations
  9. which correlates more with cognitive defects in AD (NFT or amyloid)?
  10. what are PHF
    paired helical fragments (poorly soluble tau)
  11. alpha secretase and BACE2
    occur in nonneural tissue to prevent AB peptide formation
  12. what does y-secretase include and what else does it cleave?
    • PS, nicastrin, aph-1 and pen-2
    • cleaves Notch1
    • PS1-/- bad b/c Notch1, though decreased in levels of ab
  13. BACE -/-
    viable but b secretes required to generate N-terminis fragment which meant without it individuals had behavioral and metabolic abnormalities.
  14. APP-/-
    viable, function redundancy by APLP
  15. flurizan (GSM)
    • modulator/inhibitor of y-secretase activity
    • anti-inflammatory drug
    • decrease levels of ab42 w/o impacting cleave sites
  16. low density lipoprotein receptor related protein
    promotes clearance of AB from brain by soluble circulating LRP acting as sink for Ab in plasma
  17. over expression of Low density lipoprotein receptor
    binds to APOE to decrease amyloid and enhance clearance of ab
  18. what does neurofibrilary tangles look like
    flame shaped in pyramidal neurons
  19. why is PET not as widely used as SPECT
    costly and limited availability
  20. PIB
    amyloid binding PET radiotracers: retention in neocortical areas (frontal and cortical), temporal and parietal
  21. F-FDDNP
    bind NFT and plaques (higher in hippocampus and amygdala)
  22. agonist
    activates activity through similar protein
  23. protofibrils
    • intermediates of synthetic ab
    • toxic
  24. mutations after y-secretase cleavage site
    larger self-aggregating AB42
  25. intraspection
    looking within and aware of own confusion
  26. flurbiprofen
  27. Elan's monoclonal antibody
    • oligomerization (raise them against AB6 to decrease toxicity
    • AB fibers are not toxic
  28. what were the side effects of prisoners on vaccine for ab subunit?
    central pontine myelinolysis (break b/c of bursting of water)
  29. amyloidosis
    any disease related to abnormal folding of protein that results in formation of fibers called amyloids (may not be toxic cause tissue to not function properly)
  30. 5 phases of clinical trials
    • 0: subtherapetuic dose¬†(10-15 people)¬†preliminary data what drug does to body
    • 1: 20-80 people; look at safety, side effects
    • 2: 100-300 people; effective and safety
    • 3: 1000-3000 confirm effectiveness, find effective dose (side effect)
    • 4: drug company monitor/obtain info about optimal use of drug
  31. biomarkers
    body fluid or skin biopsy, imaging provide markers for diagnosis
  32. where does AD initially attack
    hippocampus (20 years before diagnosis)
  33. FDG
    analog of glucose, where blood flow is a lot of activity, a lot of glucose metabolism in that region
  34. where does PET look at?
    look at brain function (metabolism, perfusion)
  35. cerebellum
    balance (lose balance when running for alice)
  36. entorhinal cortex
    memory and navigation
  37. temporal lobe
    language comprehension, emotion (hippocampus and hypothalamus)
  38. frontal lobe
    speech, planning, problem solving
  39. parietal
    spatial orientation
  40. occiptial
    visual, smell, last place to be affected
  41. fronto-temporal disease
    behavioral rather than short term memory
  42. what kind of secondary structure are in fibers
    beta sheets, h bonds in between
  43. what was used in the study to det stable units of tau?
    • SEC
    • FCS (fluorescence correlated spectroscopy)
    • Western blot
    • mass spec
  44. what did the SDS page and western blot show?
    oligomeric species (composed of untruncated RD monomer)
  45. micro bca point
    • to avoid differential labeling
    • tau assemblies incorporated label equivalently
  46. FCS
    • confirm size estimates
    • rule out heterogeneity
  47. which aa can be phosphorylated?
    Ser and Thr
  48. weight of amino acid and monomer
    110 Da, 4kDa
  49. how does ab multimer disrupt lipid bilayer
    cause Ca2+ homeostasis to decrease
  50. dutch mutation
    blood vessels increase in AB, weakening of cerebral blood vessel, more diffuse plaques
  51. prodromal
    appearance of first symptoms and full development of symptoms
  52. susceptibility locus
    ApoE may or may not cause disease
  53. liposome
    • not four in nature
    • spherical shapes
  54. how many repeat units in tau
    • 3 or 4
    • highly pos charged
  55. transcelluar propagation
    taking in as abnormal and causing others to "tram plate directed conformational change"
  56. morris water maze
    cognitively impaired mice take long time to find platform
  57. MMSE
    • mini mental state exam
    • 30 Qs
Card Set
notes AD
AD midterm 1