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. 1994 Nov 8;91(23):11183–11186. doi: 10.1073/pnas.91.23.11183

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

W J Strittmatter 1, A M Saunders 1, M Goedert 1, K H Weisgraber 1, L M Dong 1, R Jakes 1, D Y Huang 1, M Pericak-Vance 1, D Schmechel 1, A D Roses 1
PMCID: PMC45191  PMID: 7972031

Abstract

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

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Selected References

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