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• Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid beta-peptide deposition in homozygous APP(V717F) transgenic mice.
• Citation:
  Irizarry M, Cheung B, Rebeck G, Paul S, Bales K, Hyman B
  

  Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid beta-peptide deposition in homozygous APP(V717F) transgenic mice.

  Acta neuropathologica. 2000 Nov;100(5):451-8
  [PubMed] [Alzforum]
• Supporting:
  • APOE4 causes increased deposition of Aβ in the entorhinal cortex.

    SHOW Details   Supporting(5)   Consistent(1)     Genes/Proteins: (3)

    Description: From an anatomical perspective is it worth noting that neurons of the entorhinal cortex send their axons to the molecular layer of the dentate gyrus, a layer observed to have high concentration of Aβ deposition, and severing these axons causes decreased deposition. Other mechanisms linking APOE4 to Aβ have been proposed.
    Experimental Approach: Mechanism - physiological systems,   Genetics,   Mechanism - biochemistry and structural biology,   Biomarkers
    Pathogenic Narrative Tags: Initial condition
    Supporting Evidence
    

    • Ye S, Huang Y, Müllendorff K, Dong L, Giedt G, Meng E, Cohen F, Kuntz I, Weisgraber K, Mahley R
      Apolipoprotein (apo) E4 enhances amyloid beta peptide production in cultured neuronal cells: apoE structure as a potential therapeutic target.
      Proceedings of the National Academy of Sciences of the United States of America. 2005 Dec 20;102(51):18700-5
    • Reilly J, Games D, Rydel R, Freedman S, Schenk D, Young W, Morrison J, Bloom F
      Amyloid deposition in the hippocampus and entorhinal cortex: quantitative analysis of a transgenic mouse model.
      Proceedings of the National Academy of Sciences of the United States of America. 2003 Apr 15;100(8):4837-42
    • Irizarry M, Rebeck G, Cheung B, Bales K, Paul S, Holzman D, Hyman B
      Modulation of A beta deposition in APP transgenic mice by an apolipoprotein E null background.
      Annals of the New York Academy of Sciences. 2000;920:171-8
    • Irizarry M, Cheung B, Rebeck G, Paul S, Bales K, Hyman B
      Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid beta-peptide deposition in homozygous APP(V717F) transgenic mice.
      Acta neuropathologica. 2000 Nov;100(5):451-8
    • Buxbaum J, Thinakaran G, Koliatsos V, O'Callahan J, Slunt H, Price D, Sisodia S
      Alzheimer amyloid protein precursor in the rat hippocampus: transport and processing through the perforant path.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 1998 Dec 1;18(23):9629-37

    Consistent statements
    

    • ApoE4 alleles, which increase risk of AD, also increase Aβ accumulation. Lambert M  Barlow A  Chromy B  Edwards C  Freed R  Liosatos M  Morgan T  Rozovsky I  Trommer B  Viola K  Wals P  Zhang C  Finch C  Krafft G  Klein W 

    Genes/Proteins
    

    • Protein: Beta-amyloid protein 42 [Homo sapiens]
    • Protein: Beta-amyloid protein 40 [Homo sapiens]
    • Protein: Apolipoprotein E [Homo sapiens]
  • The fact that APP transgenic mice that are Apoe-/- develop Aβ deposits in a different anatomical distribution suggests that apoE is involved in extracellular Aβ transport.

    SHOW Details   Supporting(3)   Consistent(1)   Alternative to: (2)    Genes/Proteins: (6)

    Experimental Approach: Genetics,   Animal models,   Pathophysiology,   Mechanism - physiological systems,  
    Pathogenic Narrative Tags: Perturbation Initial condition
    Supporting Evidence
    

    • Holtzman D, Bales K, Wu S, Bhat P, Parsadanian M, Fagan A, Chang L, Sun Y, Paul S
      Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease.
      The Journal of clinical investigation. 1999 Mar;103(6):R15-R21
    • Irizarry M, Cheung B, Rebeck G, Paul S, Bales K, Hyman B
      Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid beta-peptide deposition in homozygous APP(V717F) transgenic mice.
      Acta neuropathologica. 2000 Nov;100(5):451-8
    • Bales K, Verina T, Dodel R, Du Y, Altstiel L, Bender M, Hyslop P, Johnstone E, Little S, Cummins D, Piccardo P, Ghetti B, Paul S
      Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition.
      Nature genetics. 1997 Nov;17(3):263-4

    Consistent statements
    

    • ApoE may be influencing Aβ deposition through clearance of Aβ, by altering the metabolic pathway by which Aβ is removed from the brain via apoE-containing lipoprotein sequestration of soluble Aβ. Holtzman D 

    Alternative statements
    

    • ApoE-/- decreased amyloid A (AA) deposition in human and mouse spleen. Holtzman D 
    • Inhibition of Aβ fibrillogenesis due to absence of endogenous ApoE was not due to a change in ratio of Aβ42:total Aβ. Holtzman D 

    Genes/Proteins
    

    • Gene: APP amyloid beta (A4) precursor protein [Homo sapiens]
    • Protein: Beta-amyloid protein 42 [Homo sapiens]
    • Protein: Beta-amyloid protein 40 [Homo sapiens]
    • Protein: Apolipoprotein E [Mus musculus]
    • Gene: Apoe apolipoprotein E [Mus musculus]
    • Protein: Amyloid beta A4 protein [Homo sapiens]
• Created On: Wed, Apr 23 06:39:16 EDT 2008
• Last Modified On: Wed Apr 23 06:39:16 EDT 2008