complex diseases part 1.txt

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complex diseases part 1.txt
2013-04-29 18:54:49
complex diseases part

complex diseases part 1.txt
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  1. What is Alzheimer’s Disease and name 2 of the genes involved and what results from their mutation?
    • Neurodegenerative disease affecting long and short term memory, Cognitive functions, behavior and motor skills.
    • Mechanism of Alzheimers: Beta-amyloid buildup and tau tangles
    • The two genes involved (Familial AD):
    • 1. APP: Normal gene product is Amyloid-beta A4 protein. A mutation in this gene Changes location of ALPHA secretase cleavage site, leading to INcrease in BETA cleavage occurrence = increase in AB42 production.
    • 2. PSEN1 and PSEN2: these mutations cause a change in GAMMA secretase and shifts APP towards AB42 production.
  2. Describe how APP can be differentially processed and identify the resulting products. (ie, What is responsible for the processing of APP, how does it result in different products etc...)
    • Two pathways (one healthy, one not):
    • 1. Alpha: healthy pathway, in which APP cleaved by Alpha secretase, then gamma secretase. After these are cleaved, p3 subunit is released
    • 2. Beta: DISEASE causing, in which APP cleaved by beta secretase, then gamma secretase. The end result is ABeta42 production. This ABeta42 is what causes the buildup of plaque in the brain.
  3. What is PET and how is it used? How can it help diagnose a patient with AD?
    • PET stands for POSITON EMISSION TOMOGRAPHY. This produces a 3D image of parts of the body to identify various functions. In relation to AD, it measures glucose metabolism and Abeta deposits in the BRAIN.
    • In diagnosis, there are two markers:
    • 1. DECREASE in glucose metabolism in the brain: FDG-PET used
    • 2. INCREASE in Abeta deposits in brain: PIB-PET used
  4. What are the PET findings when comparing the brain of an unaffected elderly patient with the brain of an AD patient?
    • 1. DECREASE in glucose metabolism in the brain: FDG-PET used
    • 2. INCREASE in Abeta deposits in brain: PIB-PET used.
    • PET showed shrinking of brain tissue and neural and synaptic brain loss in AD patient vs control
  5. What were the methods used in the study of Clinical and Biomarker changes in Dominantly inherited Alzheimer’s disease?
    • 6 Methods used:
    • 1. Clinical biomarkers: including family and medical history*
    • 2. Cognitive assessment: Dementia rating, based on mental state and memory
    • 3. MRI: used to detect brain atrophy
    • 4. FDG-PET: used to analyze cerebral glucose metabolism
    • 5. PIB-PET: look at Abeta deposits in brain (increase meaning AD)
    • 6. Biochemical measures: look at Ab42 and tau proteins
  6. What are these AD Clinical and Biomarkers and what was the relative order of the changes before ADAD onset? Describe how these biomarkers change over time.
    • 1. Clinical Dementia rating-Sum of boxes: CDR = 0 for cognitive function, and 18 is MAX cognitive impairment
    • 2. Mini-mental state exam: 30 indicates NO impairment, 0 = SEVERE impairment
    • 3. Wechsler Memory Scale-Revised Logical memory: 0 = NO recall of memory, 25 = complete recall (from 25 bits of info)
    • Other levels were tested in laboratory:
    • DECREASE in cerebral glucose metabolism over time
    • INCREASE in Ab42 in plasma, Tau protein and brain atrophy over time