Current Brain Imaging
  1. Alzheimer's Disease (AD)
    1. Neurons
      1. Parts of
        1. Cell body - contains the nucleus that regulates the cell via its genetic materials
        2. Dendrites - branch out to other neurons sending and receiving information
        3. Axon - transmits the messages


      2. http://slideplayer.com/slide/9742228/ (not active)

    2. Chromosomes, Alleles, and genes defined
    3. Pathology of disease
      1. It appears to be a gene problem, however, the exact genetic causes has not been identified. Other associated risk factors appear with variations chromosome 19 on the allele apolipoprotein E gene (APOE)
        1. APOE ε2 - rare and may prevent early onset on disease
        2. APOE ε3 - doesn't appear to either increase or decrease the probability of disease
        3. APOE ε4 - risk increases and usually appears early. However, some people that have this anomaly may never get AD, while other that don't have this allele get AD
      2. Other risk
        1. Mutations with chromosomes: 1, 14, and 21
          1. Presenilin 1 (gene) on chromosome 14 creates abnormal proteins
          2. Presenilin 2 (gene) on chromosome 1 creates abnormal proteins
          3. These create amyloid plaque
        2. Early onset occurs between 30 to mid 60s at less than 10% of the AD population
        3. If a mother or father has early onset, the child has ~50%
        4. Many other factors may also contribute, such as: stroke, high blood pressure, diet, mental stimulation, etc..
        5. Again the exact cause is still under investigation

      3. These genes generate protein for cell construction, operation, and repair. It appears that these abnormal genes generate proteins that may cause AD. As an example
        1. Chromosome 21 forms abnormal amyloid precursor protein (APP) and/or
        2. Chromosome 14 creates a mutation of presenilin 1
        3. Chromosome 1 creates a mutation of presenilin 2
        4. These mutations breakdown APP, but in an abnormal way, by generating amyloid plaque
      4. Neurofibrillary tangles
        1. Generated from tau, which is an abnormal protein that is formed by hyperphosphorylation
        2. Normally microtubles are formed within the nerve cell which transports information within the cell
        3. These abnormal tangles cause the microtubles to collapse
        4. Tau formation is normal unless hyperphosphorylation occurs
        5. There are other diseases associated with hyperphosphorylation of microtubles
  2. Imaging AD via nuclear medicine
    1. There are three different agents approved for imaging AD


      https://basicmedicalkey.com/dementia-and-its-treatment/

      1. First you may recall what AD looks like when imaging with FDG
        1. Atrophy causes reduced uptake of the radio tracer
        2. Initially effecting the parietal and temporal lobes in a bilateral fashion
        3. As AD progress reduced uptake occurs in the frontal areas of the brain
        4. It is important that you understand the difference between Amyvid and FDG!


        2. https://www.medscape.com/viewarticle/762347

      2. 18F-florbetapir (Amyvid from Eli Lilly) The greater the plaque the greater the uptake
        1. Is a peptide that has an affinity for β-Amyloid plaque
        2. The greater the plaque the greater the uptake
        3. Dose is 10 mCi, delayed images start 20 to 50 minuts post dose, acquire data for 10 minutes on a single bed

      3. 18F-flutemetamol (Vizamyl from GE Healthcare)
        1. This is a thioflavin derivative ot "Pittsburg compound B (PiB)
        2. Will specificially attach to β-Amyloid plaque
        3. 5 mCi dose, delayed image starts 45 to 180 minutes post dose, acquire a single bed position for 15 to 20 minutes

      4. 18F-florbetaben (NeuraCeq from Piramal Pharma)
        1. This agent was 100 sensitive and 92% specific in detecting AD
        2. Is a stilbene derivative
        3. Has an affinity β-Amyloid plaque
        4. 8 mCi dose, delayed images start 90 post dose, acquire single bed position for 20 minutes

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Reference

NIH - "Alzheimer's Disease Genetic Fact Sheet" - https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet

BrightFocus Foundation - Amyloid Plaques and Neurofibrillary Tangles - https://www.brightfocus.org/alzheimers-disease/infographic/amyloid-plaques-and-neurofibrillary-tangles