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Cited by 1,459

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease.

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Kosik, K S, Joachim, C L, Selkoe, D J·1986·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.83.11.4044
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Abstract

The detailed protein composition of the paired helical filaments (PHF) that accumulate in human neurons in aging and Alzheimer disease is unknown. However, the identity of certain components has been surmised by using immunocytochemical techniques. Whereas PHF share epitopes with neurofilament proteins and microtubule-associated protein (MAP) 2, we report evidence that the MAP tau (tau) appears to be their major antigenic component. Immunization of rabbits with NaDodSO4-extracted, partially purified PHF (free of normal cytoskeletal elements, including tau) consistently produces antibodies to tau but not, for example, to neurofilaments. Such PHF antibodies label all of the heterogeneous fetal and mature forms of tau from rat and human brain. Absorption of PHF antisera with heat-stable MAPs (rich in tau) results in almost complete loss of staining of neurofibrillary tangles (NFT) in human brain sections. An affinity-purified antibody to tau specifically labels NFT and the neurites of senile plaques in human brain sections as well as NaDodSO4-extracted NFT. tau-Immunoreactive NFT frequently extend into the apical dendrites of pyramidal neurons, suggesting an aberrant intracellular locus for this axonal protein. tau and PHF antibodies label tau proteins identically on electrophoretic transfer blots and stain the gel-excluded protein representing NaDodSO4-insoluble PHF in homogenates of human brain. The progressive accumulation of altered tau protein in neurons in Alzheimer disease may result in instability of microtubules, consequent loss of effective transport of molecules and organelles, and, ultimately, neuronal death.

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Metadata

Authors
Kosik, K. S., Joachim, C. L., & Selkoe, D. J.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
1986-06
Volume
83
Issue
11
Pages
4044-4048
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.83.11.4044
OpenAlex
W2060458492
Cited by
1,459
References
1
FWCI
54.03
Type
journal article
Language
en
Open access
green

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