Heterogeneity of tau proteins in Alzheimer's disease

Evidence for increased expression of an isoform and preferential distribution of a phosphorylated isoform in neurites

Wan Kyng Liu, Dennis W Dickson, Shu Hui Yen

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40 Citations (Scopus)

Abstract

PHF-tau, a modified form of tau in Alzheimer diseased brains, is composed of proteins of molecular weight 68, 64, and 60 kd. The 68-kd PHF-tau has been reported to be encoded by a tau transcript containing both exons 2 and 3. The 64-kd protein contains exon 2, but not exon 3, and the 60-kd protein contains neither exons 2 nor 3. To study the proportion of different tau isoforms in PHF-tau and normal tau, we raised antibodies to exon 2 (E-2) and exon 3 (E-3). By immunoblots, about 74% of the PHF-tau contained exon 2, and 25% contained exon 3; whereas in normal tau, 82 to 90% contained exon 2, and no more than 5% contained exon 3. Enzyme-linked immunosorbent assays demonstrated that PHF-tau was 38% less reactive with E-2 and 79% more reactive with E-3 than normal tau. Alkaline phosphatase treatment increased the E-2 immunoreactivity of PHF-tau by 120% and normal tau by 38%, but it had no effect on E-3 ttimunoreactivity. The dephosphorylated PHF-tau and normal tau were similar in E-2 immunoreactivities. Phosphatase treatment of Alzheimer's diseased brain sections increased the number of E-2 immunoreactive neuropil threads and senile plaque neurites but had very little effect on the number of immunoreactive neuroflbrillary tangles. The results suggest that PHF-tau contains proportionally more isoforms with E-3 than normal tau; that the E-2 epitope is more Phosphorylated in PHF-tau than in normal tau; and that the phosphorylated E-2 epitope of PHF-tau is preferentially located in neurites.

Original languageEnglish (US)
Pages (from-to)387-394
Number of pages8
JournalAmerican Journal of Pathology
Volume142
Issue number2
StatePublished - Feb 1993
Externally publishedYes

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tau Proteins
Neurites
Exons
Alzheimer Disease
Protein Isoforms
Epitopes
Neuropil Threads
Proteins
Amyloid Plaques
Brain
Phosphoric Monoester Hydrolases
Alkaline Phosphatase
Molecular Weight
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

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title = "Heterogeneity of tau proteins in Alzheimer's disease: Evidence for increased expression of an isoform and preferential distribution of a phosphorylated isoform in neurites",
abstract = "PHF-tau, a modified form of tau in Alzheimer diseased brains, is composed of proteins of molecular weight 68, 64, and 60 kd. The 68-kd PHF-tau has been reported to be encoded by a tau transcript containing both exons 2 and 3. The 64-kd protein contains exon 2, but not exon 3, and the 60-kd protein contains neither exons 2 nor 3. To study the proportion of different tau isoforms in PHF-tau and normal tau, we raised antibodies to exon 2 (E-2) and exon 3 (E-3). By immunoblots, about 74{\%} of the PHF-tau contained exon 2, and 25{\%} contained exon 3; whereas in normal tau, 82 to 90{\%} contained exon 2, and no more than 5{\%} contained exon 3. Enzyme-linked immunosorbent assays demonstrated that PHF-tau was 38{\%} less reactive with E-2 and 79{\%} more reactive with E-3 than normal tau. Alkaline phosphatase treatment increased the E-2 immunoreactivity of PHF-tau by 120{\%} and normal tau by 38{\%}, but it had no effect on E-3 ttimunoreactivity. The dephosphorylated PHF-tau and normal tau were similar in E-2 immunoreactivities. Phosphatase treatment of Alzheimer's diseased brain sections increased the number of E-2 immunoreactive neuropil threads and senile plaque neurites but had very little effect on the number of immunoreactive neuroflbrillary tangles. The results suggest that PHF-tau contains proportionally more isoforms with E-3 than normal tau; that the E-2 epitope is more Phosphorylated in PHF-tau than in normal tau; and that the phosphorylated E-2 epitope of PHF-tau is preferentially located in neurites.",
author = "Liu, {Wan Kyng} and Dickson, {Dennis W} and Yen, {Shu Hui}",
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T2 - Evidence for increased expression of an isoform and preferential distribution of a phosphorylated isoform in neurites

AU - Liu, Wan Kyng

AU - Dickson, Dennis W

AU - Yen, Shu Hui

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N2 - PHF-tau, a modified form of tau in Alzheimer diseased brains, is composed of proteins of molecular weight 68, 64, and 60 kd. The 68-kd PHF-tau has been reported to be encoded by a tau transcript containing both exons 2 and 3. The 64-kd protein contains exon 2, but not exon 3, and the 60-kd protein contains neither exons 2 nor 3. To study the proportion of different tau isoforms in PHF-tau and normal tau, we raised antibodies to exon 2 (E-2) and exon 3 (E-3). By immunoblots, about 74% of the PHF-tau contained exon 2, and 25% contained exon 3; whereas in normal tau, 82 to 90% contained exon 2, and no more than 5% contained exon 3. Enzyme-linked immunosorbent assays demonstrated that PHF-tau was 38% less reactive with E-2 and 79% more reactive with E-3 than normal tau. Alkaline phosphatase treatment increased the E-2 immunoreactivity of PHF-tau by 120% and normal tau by 38%, but it had no effect on E-3 ttimunoreactivity. The dephosphorylated PHF-tau and normal tau were similar in E-2 immunoreactivities. Phosphatase treatment of Alzheimer's diseased brain sections increased the number of E-2 immunoreactive neuropil threads and senile plaque neurites but had very little effect on the number of immunoreactive neuroflbrillary tangles. The results suggest that PHF-tau contains proportionally more isoforms with E-3 than normal tau; that the E-2 epitope is more Phosphorylated in PHF-tau than in normal tau; and that the phosphorylated E-2 epitope of PHF-tau is preferentially located in neurites.

AB - PHF-tau, a modified form of tau in Alzheimer diseased brains, is composed of proteins of molecular weight 68, 64, and 60 kd. The 68-kd PHF-tau has been reported to be encoded by a tau transcript containing both exons 2 and 3. The 64-kd protein contains exon 2, but not exon 3, and the 60-kd protein contains neither exons 2 nor 3. To study the proportion of different tau isoforms in PHF-tau and normal tau, we raised antibodies to exon 2 (E-2) and exon 3 (E-3). By immunoblots, about 74% of the PHF-tau contained exon 2, and 25% contained exon 3; whereas in normal tau, 82 to 90% contained exon 2, and no more than 5% contained exon 3. Enzyme-linked immunosorbent assays demonstrated that PHF-tau was 38% less reactive with E-2 and 79% more reactive with E-3 than normal tau. Alkaline phosphatase treatment increased the E-2 immunoreactivity of PHF-tau by 120% and normal tau by 38%, but it had no effect on E-3 ttimunoreactivity. The dephosphorylated PHF-tau and normal tau were similar in E-2 immunoreactivities. Phosphatase treatment of Alzheimer's diseased brain sections increased the number of E-2 immunoreactive neuropil threads and senile plaque neurites but had very little effect on the number of immunoreactive neuroflbrillary tangles. The results suggest that PHF-tau contains proportionally more isoforms with E-3 than normal tau; that the E-2 epitope is more Phosphorylated in PHF-tau than in normal tau; and that the phosphorylated E-2 epitope of PHF-tau is preferentially located in neurites.

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