Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease.

• DOI: 10.1073/pnas.91.23.11183
• Publication Date: 2006-05-31T08:59:11Z
• Authors: W J Strittmatter; A M Saunders; M Goedert; K H Weisgraber; L M Dong; R Jakes; D Y Huang; M Pericak-Vance; D Schmechel; A D Roses
• Keywords: Tau protein; Apolipoprotein E; Neurofibrillary tangle

The apolipoprotein E (apoE) type 4 allele (APOE4) is a susceptibility gene for late-onset familial and sporadic Alzheimer disease. ApoE found in some neurofibrillary tangle-bearing neurons, one of the major pathologic hallmarks Neurofibrillary tangles contain paired helical filaments formed from hyperphosphorylated microtubule-associated protein tau. In vitro, tau binds avidly to apoE3, but not apoE4, forming bimolecular complex. Tau phosphorylated with brain extract does bind either isoform. ApoE3 microtubule-binding repeat region tau, which also that thought cause self-assembly into filament. Binding studies fragments demonstrate tau-binding apoE3 corresponds its receptor-binding domain distinct lipoprotein particles or beta/A4 peptide. Isoform-specific interactions apoE may regulate intraneuronal metabolism disease alter rate formation tangles.