The impact of a novel apolipoprotein E and amyloid-β protein precursor-interacting protein on the production of amyloid-β

J Alzheimers Dis. 2011;26(2):239-53. doi: 10.3233/JAD-2011-102115.


Alzheimer's disease (AD) is characterized by disrupted metabolism of the amyloid-β protein precursor (AβPP) and deposition of a byproduct, the amyloid-β (Aβ) peptide, into plaques. AD is also genetically linked to the gene for apolipoprotein E (apoE). We have identified a novel apoE-binding protein (TMCC2) that also forms a complex with AβPP. TMCC2 is a neuronal, predominantly ER-localized, protein that co-migrated with AβPP during native gel electrophoresis of rat brain extracts, and co-immunoprecipitated with AβPP from transfected human cell lysates. TMCC2 bound apoE in an isoform-specific manner in vitro and co-immunoprecipitated with apoE from cell lysates. Co-expression of apoE and TMCC2 stimulated Aβ production from the "Swedish" variant of AβPP (K595 M/N596L) by up to 1.5-fold (p < 0.05), and also from the 99-amino acid C-terminal fragment of AβPP (AβPP-C99) that is the direct precursor to Aβ by 1.5- to 2-fold (p < 0.0005), this effect was greater with apoE4 than apoE3 (p = 0.02); both apoE3 and apoE4 stimulated a greater increase in Aβ1-42 than Aβ1-40 production from AβPP-C99 in the presence of TMCC2. The interaction between TMCC2 and apoE may therefore contribute to disrupted AβPP metabolism and altered Aβ production, as observed in AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / biosynthesis*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Brain / metabolism*
  • Carrier Proteins / metabolism*
  • Humans
  • Neurons / metabolism*
  • Protein Binding / genetics
  • Rats


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Apolipoproteins E
  • Carrier Proteins