Cited by 779Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease.

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Köpke, E, Tung, Y.C., Shaikh, S, Alonso, A.C., Iqbal, K, Grundke-Iqbal, I·1993·Journal of Biological Chemistry

Abstract

The major protein subunit of the paired helical filaments (PHF) of Alzheimer disease (AD) is the microtubule-associated protein tau. Tau is a family of phosphopolypeptides that are abnormally phosphorylated in PHF. In this study, a non-PHF pool of tau abnormally phosphorylated at Ser-199/202, and tau not phosphorylated at this site (AD P-tau and AD tau, respectively) were isolated from the 27,000 x g to 200,000 x g fraction of AD brain homogenate by extraction in 8 M urea, followed by dialysis against Tris buffer. AD P-tau and AD tau were further purified and separated from each other by acid precipitation, glial fibrillary acidic protein affinity chromatography, and phosphocellulose chromatography. The resulting AD P-tau and AD tau preparations were free of cytoskeletal proteins, ubiquitin, and beta-amyloid peptide. Immunochemical and morphological analysis of AD P-tau preparations revealed that most of the protein was of non-PHF origin. The AD P-tau was about 3-4-fold (approximately 8 mol P04/mol protein, M(r) 41,318) more phosphorylated than cytosolic tau from AD and control brains. Unlike PHF, the AD P-tau lacked ubiquitin. In AD brain the levels of cytosolic tau were about half of those in control aged cases. These findings suggest that the abnormal phosphorylation of tau in AD occurs in the cytosol.

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Crossref · 10.1016/s0021-9258(20)80536-5

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Authors
Köpke, E., Tung, Y. C., Shaikh, S., Alonso, A. C., Iqbal, K., & Grundke-Iqbal, I.
Affiliations
Regeneron (United States) (US)
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1993-11
Volume
268
Issue
32
Pages
24374-24384
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1601433695
Cited by
779
References
52
Citations by year
2026: 22 · 2025: 40 · 2024: 44 · 2023: 42 · 2022: 24 · 2021: 45 · 2020: 49 · 2019: 45 · 2018: 43 · 2017: 29 · 2016: 30 · 2015: 30 · 2014: 29 · 2013: 22 · 2012: 29
FWCI
7.79
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ns018105-17, 5p01ag004220-12)
  • National Institute on Aging (F32 AGO 5541, AGO4220)
  • National Institute of Neurological Disorders and Stroke (NS 18105)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
tau protein, Alzheimer's disease, tau phosphorylation, paired helical filaments, ubiquitin
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Brain, Chromatography, Affinity, Chromatography, Ion Exchange, Electrophoresis, Polyacrylamide Gel, Humans, Microscopy, Electron, Phosphorylation, Protein Denaturation, Solubility, Ubiquitins, Urea, tau Proteins

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