Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004;5(3):205-18.
doi: 10.1385/NMM:5:3:205.

Tau phosphorylation in Alzheimer's disease: potential involvement of an APP-MAP kinase complex

Alyson L Peel  1 , Noah Sorscher, Joseph Y Kim, Veronica Galvan, Sylvia Chen, Dale E Bredesen
Affiliations

Tau phosphorylation in Alzheimer's disease: potential involvement of an APP-MAP kinase complex

Alyson L Peel et al. Neuromolecular Med. 2004.

Abstract

The two predominant pathological concomitants of Alzheimer's disease (AD) are senile plaques and neurofibrillary tangles. Although many biochemical studies have addressed the composition and formation of these AD hallmarks, very little is known about the interrelationship between the two. Here we present evidence that the tau phosphorylation characteristic of neurofibrillary tangles may be mediated by a physical association of MKK6 (mitogen-associated protein kinase kinase 6) with tau and subsequent phosphorylation of tau by the MKK6 substrate, p38 MAPK; and that APP (beta-amyloid precursor protein) may be co-immunoprecipitated both with MKK6 and its upstream MAPKKK, ASK1. Taken together with recent data demonstrating APP dimerization by beta-amyloid peptide (Abeta) (Lu et al., 2003), and the possible activation of ASK1 via APP dimerization (Hashimoto et al., 2003), these results suggest a model of AD in which Abeta peptide dimerizes APP directly, leading to the activation of ASK1, MKK6, and p38, with subsequent phosphorylation of tau at sites characteristic of AD.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Neurochem. 1999 May;72(5):2053-8 - PubMed
    1. Neurobiol Aging. 2002 Sep-Oct;23 (5):855-9 - PubMed
    1. Trends Neurosci. 1998 Oct;21(10):428-33 - PubMed
    1. Gerontology. 1990;36 Suppl 1:15-24 - PubMed
    1. Science. 2001 Aug 24;293(5534):1487-91 - PubMed

Publication types

MeSH terms

LinkOut - more resources

  NODES
Association 1
twitter 2