TY - JOUR
T1 - Heterogeneity of tau proteins in Alzheimer's disease
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
PY - 1993/2
Y1 - 1993/2
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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M3 - Article
C2 - 7679548
AN - SCOPUS:0027402861
SN - 0002-9440
VL - 142
SP - 387
EP - 394
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -