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Neighbored phosphorylation sites as PHF-tau specific markers in Alzheimer's disease.
Biochem Biophys Res Commun. 2006 Aug 04; 346(3):819-28.BB

Abstract

Neurofibrillary tangles, which represent a major pathological hallmark in Alzheimer's disease (AD), are deposits of the hyperphosphorylated microtubule-associated tau protein (PHF-tau). However, a link between the phosphorylation pattern and the cause or the progress of AD is still missing. The work reported here focused on PHF-tau specific local phosphorylation patterns at Thr212/Ser214 and Thr231/Ser235 using monoclonal antibodies (mAb) generated against correspondingly modified peptides. The binding motifs of the obtained six mAbs were characterized with non-, mono-, and double-phosphorylated peptides as well as terminally shortened sequences. Five mAbs stained neurofibrillary tangles, neuritic plaques, and neuropil threads from autoptic brains of AD cases. Four mAbs recognized PHF-tau without significant cross-reactivity towards normal human tau, bovine tau, and dephosphorylated PHF-tau in ELISA and Western blot analysis. Thus, double phosphorylation is sufficient to distinguish PHF-tau from all other tau versions and there is no need to postulate any PHF-tau specific conformation for this region.

Authors+Show Affiliations

Bioanalytics, Center for Biotechnology and Biomedicine (BBZ), Faculty of Chemistry and Mineralogy, University of Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16781671

Citation

Singer, David, et al. "Neighbored Phosphorylation Sites as PHF-tau Specific Markers in Alzheimer's Disease." Biochemical and Biophysical Research Communications, vol. 346, no. 3, 2006, pp. 819-28.
Singer D, Lehmann J, Hanisch K, et al. Neighbored phosphorylation sites as PHF-tau specific markers in Alzheimer's disease. Biochem Biophys Res Commun. 2006;346(3):819-28.
Singer, D., Lehmann, J., Hanisch, K., Härtig, W., & Hoffmann, R. (2006). Neighbored phosphorylation sites as PHF-tau specific markers in Alzheimer's disease. Biochemical and Biophysical Research Communications, 346(3), 819-28.
Singer D, et al. Neighbored Phosphorylation Sites as PHF-tau Specific Markers in Alzheimer's Disease. Biochem Biophys Res Commun. 2006 Aug 4;346(3):819-28. PubMed PMID: 16781671.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neighbored phosphorylation sites as PHF-tau specific markers in Alzheimer's disease. AU - Singer,David, AU - Lehmann,Jörg, AU - Hanisch,Katja, AU - Härtig,Wolfgang, AU - Hoffmann,Ralf, Y1 - 2006/06/09/ PY - 2006/05/22/received PY - 2006/05/29/accepted PY - 2006/6/20/pubmed PY - 2006/8/22/medline PY - 2006/6/20/entrez SP - 819 EP - 28 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 346 IS - 3 N2 - Neurofibrillary tangles, which represent a major pathological hallmark in Alzheimer's disease (AD), are deposits of the hyperphosphorylated microtubule-associated tau protein (PHF-tau). However, a link between the phosphorylation pattern and the cause or the progress of AD is still missing. The work reported here focused on PHF-tau specific local phosphorylation patterns at Thr212/Ser214 and Thr231/Ser235 using monoclonal antibodies (mAb) generated against correspondingly modified peptides. The binding motifs of the obtained six mAbs were characterized with non-, mono-, and double-phosphorylated peptides as well as terminally shortened sequences. Five mAbs stained neurofibrillary tangles, neuritic plaques, and neuropil threads from autoptic brains of AD cases. Four mAbs recognized PHF-tau without significant cross-reactivity towards normal human tau, bovine tau, and dephosphorylated PHF-tau in ELISA and Western blot analysis. Thus, double phosphorylation is sufficient to distinguish PHF-tau from all other tau versions and there is no need to postulate any PHF-tau specific conformation for this region. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/16781671/Neighbored_phosphorylation_sites_as_PHF_tau_specific_markers_in_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(06)01255-1 DB - PRIME DP - Unbound Medicine ER -