AlzSWAN Knowledge Base

Powered by SWAN (Semantic Web Applications in Neuromedicine)

• Neuronal overexpression of APPL, the Drosophila homologue of the amyloid precursor protein (APP), disrupts axonal transport.
• Citation:
  Torroja L, Chu H, Kotovsky I, White K
  

  Neuronal overexpression of APPL, the Drosophila homologue of the amyloid precursor protein (APP), disrupts axonal transport.

  Current biology : CB. 1999 May 6;9(9):489-92
  [PubMed] [Alzforum]
• Supporting:
  • A number of papers report that APP overexpression and presenilin mutations can induce serious abnormalities in axonal transport in the absence of plaque formation or human Aβ. These findings and those of Meyer-Luehmann et al. are not in conflict and may in some sense be complementary.

    SHOW Details   Supporting(4)   Consistent(4)   Inconsistent(1) 

    Experimental Approach: Animal models,   Genetics,   Pathophysiology
    Pathogenic Narrative Tags: Pathogenic event Pathologic change
    Supporting Evidence
    

    • Salehi A, Delcroix J, Belichenko P, Zhan K, Wu C, Valletta J, Takimoto-Kimura R, Kleschevnikov A, Sambamurti K, Chung P, Xia W, Villar A, Campbell W, Kulnane L, Nixon R, Lamb B, Epstein C, Stokin G, Goldstein L, Mobley W
      Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration.
      Neuron. 2006 Jul 6;51(1):29-42
    • Pigino G, Morfini G, Pelsman A, Mattson M, Brady S, Busciglio J
      Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2003 Jun 1;23(11):4499-508
    • Gunawardena S, Goldstein L
      Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila.
      Neuron. 2001 Nov 8;32(3):389-401
    • Torroja L, Chu H, Kotovsky I, White K
      Neuronal overexpression of APPL, the Drosophila homologue of the amyloid precursor protein (APP), disrupts axonal transport.
      Current biology : CB. 1999 May 6;9(9):489-92

    Consistent statements
    

    • Amyloid accumulation is not an obligatory feature of dementia or neurodegeneration because neurodegenerative dementias lacking amyloid pathology (e.g., FTD) have been well described. Shen J  Kelleher R 
    • AD transgenic models suggest that reduced axonal transport rate occurs before plaque formation. Bartzokis G 
    • The idea that areas with a high density of dystrophies would be a prime location for plaque development was tested over days to weeks, but observations at sites containing dystrophies but no plaques failed to demonstrate a new plaque appearing at a site of high dystrophic neurite density, although the number of observations was relatively small. Meyer-Luehmann M  Spires-Jones T  Prada C  Garcia-Alloza M  de Calignon A  Rozkalne A  Koenigsknecht-Talboo J  Holtzman D  Bacskai B  Hyman B 
    • Increased production of wild type APP (in Trisomy 21 and other genetic triplications) and increased intracellular oligomeric Aβ can degrade axonal transport, and cause deficits in myelin development and cognition in several animal models. Bartzokis G 

    Inconsistent statements
    

    • Disease-causing mutations of EOAD in presenilin1 and 2 have a primary effect on Aβ processing and plaque formation. Small S  Duff K 
• Created On: Wed, Apr 23 06:56:51 EDT 2008
• Last Modified On: Wed Apr 23 06:56:51 EDT 2008