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Lary Walker Introduction Webinar

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Presentation made at the Alzforum's live webinar of December 5, 2016, titled "Is Alzheimer’s Disease a Uniquely Human Disorder?" - review additional information and recording at www.alzforum.org/

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Lary Walker Introduction Webinar

  1. 1. Is Alzheimer’s Disease a Uniquely Human Disorder? Lary Walker Cynthia Lemere Marc Dhenain Patrick Hof Elizabeth Head Peter Nelson Moderator: Tom Fagan Alzforum, Wednesday, December 7, 12 p.m. U.S. Eastern time
  2. 2. Aged Rhesus monkeyHuman AD Aβ
  3. 3. Walker and Jucker, in prep Human AD Aged Rhesus monkey Aβ Tau
  4. 4. 1 695Aβ Sequence of Aβ, tau? APP695 sequence identity to human: Chimpanzee: 100% Rhesus monkey: 100% [Mouse: 96.8%] E2 E2 E3 E10 E10 E10 All 6 isoforms and all major phospho sites present in simians Tau longest isoform identity to human: Chimpanzee: 100% Rhesus monkey: 98% [Mouse: 88%] After Levy et al. 1995, Uniprot; Brunden et al., 2009; Nelson et al., 1996; Holzer et al., 2004
  5. 5. Human (Homo sapiens) Mouse lemur (Microcebus murinus) Squirrel monkey (Saimiri sciureus) Rhesus macaque (Macaca mulatta) Chimpanzee (Pan troglodytes) Lifespan? 25 50 75 100 125 Years Onset of Aβ deposition ( ) in primates is proportional to lifespan After Finch and Sapolsky, 1999
  6. 6. Fibrillization Soluble protein Strain 1 Misfolding and aggregation Strain 2Amino acid differences Truncations Local environmental factors Proteopathic strains? Ann Rev Genet 2016 Amyloid
  7. 7. Something else? -ApoE -Proteostatic controls -Post-translational modifications -Biometals -Inflammation -Metabolic / cardiovascular state -Environment: Life-long activity levels Stress Diet / Microbiome …
  8. 8. Alzheimer’s disease (diagnostic): A state of dementia that is associated with characteristic Aβ plaques and tau tangles in the brain. Alzheimer’s dementia: The insidious onset and gradual progression of substantial impairment in learning and memory and at least one other cognitive domain that interferes with independence in everyday activities. Dementia definition modified from the Diagnostic and Statistical Manual of Mental Disorders [DSM-5] (Walker and Jucker, in prep) Definitions

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