title: ApoE3 binding to tau tandem repeat I is abolished by tau serine262 phosphorylation.
abstract: The risk of Alzheimer's disease is determined, in part, by inheritance of specific alleles of ApoE. Isoform specific interactions of ApoE have been shown with the microtubule-associated protein tau, which forms the neurofibrillary tangle in this disease. Synthetic peptides representing each of the four microtubule-binding domains of tau more avidly bind ApoE3 than ApoE4. Phosphorylation of serine262 in domain I of tau decreases tau binding to microtubules and also abolishes binding by ApoE3. Understanding the molecular mechanisms of the high avidity, isoform-specific interactions of ApoE with tau may help in developing approaches for disease intervention.
authors.affiliation: Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: D Y
authors.initials: DY
authors.lastname: Huang
authors.forename: K H
authors.initials: KH
authors.lastname: Weisgraber
authors.forename: M
authors.initials: M
authors.lastname: Goedert
authors.forename: A M
authors.initials: AM
authors.lastname: Saunders
authors.forename: A D
authors.initials: AD
authors.lastname: Roses
authors.forename: W J
authors.initials: WJ
authors.lastname: Strittmatter
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D012694:Serine / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D016875:tau Proteins; D012694:Serine