Summary: Amyloid Precursor Protein Processing And Alzheimer’S Disease

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PLEASE KNOW!!! There are just 28 flashcards and notes available for this material. This summary might not be complete. Please search similar or other summaries.

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  • 1 History of Alzheimer's Disease

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  • What was the first reported case of Alzheimer's Disease?

    The presence of two distinctive pathologies (neurofibrillary tangles and neuritic plaques) in the brain of a woman who had died from progressive behavioural and cognitive disorder.
  • When was Alzheimer's Disease considered to be a true distinctive disease?

    When the presence of neuritic plaques where linked to the incidence of dementia.
  • 2 RELATIONSHIP OF BRAIN Aβ ACCUMULATION TO DEMENTIA IN HUMAN PATHOLOGIC SPECIMENS

  • Is the accumulation of amyloid beta caused by dying neurons?

    Not necessarily, it comes into the extracellular matrix after nerve injury, but does not correlate with the age-expected neural degradation in other neurodegenerative disease like Parkinson's disease and frontotemporal dementia.
  • What can be generalised from the brain pathology of demented elderly?

    They may have mixed pathologies including
    • neuritic plaques
    • neurofibrillary tangles
    • Lewy bodies
    • atherosclerosis 
  • 3 STRUCTURE AND FUNCTION OF APP

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  • What is the function of APP?

    overexpression may benefit cell health and growth
    it may be important in embryonic neural migration
    it may benefit synaptic density
  • What is the function of the amyloid beta peptide?

    It influences regulation of synaptic physiology (scaling and vesicle release)
  • 4 AMYLOID PRECURSOR PROTEIN PROCESSING

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  • In which cells is APP metabolised?

    In neurons
  • What are the pathways that proteolyse APP?


    • ER --> Golgi --> synaptic terminal --> TGN --> cell surface --> proteolysed by a secretase and g secretase
    • ER --> Golgi --> synaptic terminal --> TGN --> cell surface --> internalized into endosome --> proteolysed by BACE1 and g secretase --> amyloid b secretion
    • ER --> Golgi --> synaptic terminal --> TGN --> cell surface --> internalized into endosome --> proteolysed by BACE1 and g secretase --> retromers to the TGN
    • ER --> Golgi --> synaptic terminal --> TGN --> endosomal compartment
  • How can secretion of amyloid beta best be prevented?

    By preventing cell surface endocytosis.
  • What kind of enzyme is BACE1?

    a transmembrane aspartic protease, involved in the pathogenic pathway of APP proteolysis.
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