Alzheimer's neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule associated proteins tau and MAP2

S. H. Yen, Dennis W Dickson, A. Crowe, M. Butler, M. L. Shelanski

Research output: Contribution to journalArticle

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Abstract

Ten monoclonal antibodies raised against Alzheimer's neurofibrillary tangles (ANTs) were characterized for reactivity with heat-stable microtubule fractions from bovine and human brain. Five of the antibodies showed very little reaction, but the other five reacted strongly with heat-stable microtubule associated proteins (MAPs). The proteins recognized by these antibodies have estimated molecular weights similar to those of known heat-stable MAPs, tau (52-68 kd) and MAP2 (200-250 kd). That the proteins are indeed tau and MAP2 is demonstrated by reaction of electroblotted proteins with antibodies raised in mouse and guinea pig against bovine brain tau and MAP2. One anti-ANT antibody reacts only with tau, two bind strongly to tau and weakly to MAP2, one recognizes both tau and MAP2 equally well, and one primarily stains MAP2. Extraction of ANT with 2% SDS does not remove tau or MAP2 epitopes from ANT, indicating that epitopes shared with heat-stable MAPs are integral components of ANT. The existence of tau epitopes in ANT is also demonstrated by immunoblotting of ANT-enriched fractions with anti-tau antibodies. Most of the material recognized by anti-tau antibodies in ANT-enriched fractions is present in large molecules excluded by 3% polyacrylamide gel upon electrophoresis. Anti-tau antibodies immunostain ANT in immunofluorescence and immunoperoxidase studies. The immunostaining can be blocked by absorption of anti-tau antibodies with purified tau proteins from bovine brain. Not all ANTs in any give tissue section or isolated Alzheimer perikarial preparations, however, are stained by anti-tau antibodies. These results are consistent with previous studies that have demonstrated heterogeneity of ANTs. Whether this heterogeneity is due to biochemical modification of MAPs or absence of MAPs in some ANTs is unknown. The significance of what appear to be shared epitopes recognized by monoclonal antibodies in tau and MAP2, and the implications this may have on the pathogenesis of ANT formation, requires further investigation.

Original languageEnglish (US)
Pages (from-to)81-91
Number of pages11
JournalAmerican Journal of Pathology
Volume126
Issue number1
StatePublished - 1987
Externally publishedYes

Fingerprint

Neurofibrillary Tangles
Microtubule-Associated Proteins
Epitopes
Hot Temperature
Anti-Idiotypic Antibodies
tau Proteins
Antibodies
Brain
Monoclonal Antibodies
Immunoblotting
Microtubules
Fluorescent Antibody Technique
Polyacrylamide Gel Electrophoresis
Guinea Pigs
Proteins
Coloring Agents

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Alzheimer's neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule associated proteins tau and MAP2. / Yen, S. H.; Dickson, Dennis W; Crowe, A.; Butler, M.; Shelanski, M. L.

In: American Journal of Pathology, Vol. 126, No. 1, 1987, p. 81-91.

Research output: Contribution to journalArticle

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abstract = "Ten monoclonal antibodies raised against Alzheimer's neurofibrillary tangles (ANTs) were characterized for reactivity with heat-stable microtubule fractions from bovine and human brain. Five of the antibodies showed very little reaction, but the other five reacted strongly with heat-stable microtubule associated proteins (MAPs). The proteins recognized by these antibodies have estimated molecular weights similar to those of known heat-stable MAPs, tau (52-68 kd) and MAP2 (200-250 kd). That the proteins are indeed tau and MAP2 is demonstrated by reaction of electroblotted proteins with antibodies raised in mouse and guinea pig against bovine brain tau and MAP2. One anti-ANT antibody reacts only with tau, two bind strongly to tau and weakly to MAP2, one recognizes both tau and MAP2 equally well, and one primarily stains MAP2. Extraction of ANT with 2{\%} SDS does not remove tau or MAP2 epitopes from ANT, indicating that epitopes shared with heat-stable MAPs are integral components of ANT. The existence of tau epitopes in ANT is also demonstrated by immunoblotting of ANT-enriched fractions with anti-tau antibodies. Most of the material recognized by anti-tau antibodies in ANT-enriched fractions is present in large molecules excluded by 3{\%} polyacrylamide gel upon electrophoresis. Anti-tau antibodies immunostain ANT in immunofluorescence and immunoperoxidase studies. The immunostaining can be blocked by absorption of anti-tau antibodies with purified tau proteins from bovine brain. Not all ANTs in any give tissue section or isolated Alzheimer perikarial preparations, however, are stained by anti-tau antibodies. These results are consistent with previous studies that have demonstrated heterogeneity of ANTs. Whether this heterogeneity is due to biochemical modification of MAPs or absence of MAPs in some ANTs is unknown. The significance of what appear to be shared epitopes recognized by monoclonal antibodies in tau and MAP2, and the implications this may have on the pathogenesis of ANT formation, requires further investigation.",
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