Heterogeneity of tau proteins in Alzheimer's disease. Evidence for increased expression of an isoform and preferential distribution of a phosphorylated isoform in neurites.
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 immunoreactivity. 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 neurofibrillary 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.
Liu
W K
WK
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Dickson
D W
DW
Yen
S H
SH
D000328:Adult; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000939:Epitopes; D005333:Fetus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007536:Isomerism; D016501:Neurites / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000473:pathology; D010766:Phosphorylation; D014018:Tissue Distribution; D016875:tau Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism
D000939:Epitopes; D016875:tau Proteins