Tau 3R Antibody #78129

Tau is a heterogeneous microtubule-associated protein that promotes and stabilizes microtubule assembly, especially in axons. Six isoforms with different amino-terminal inserts and different numbers of tandem repeats near the carboxy terminus have been identified, and tau is hyperphosphorylated at approximately 25 sites by Erk, glycogen synthase kinase-3 (GSK-3), and CDK5 (1,2). Phosphorylation decreases the ability of tau to bind to microtubules. Neurofibrillary tangles are a major hallmark of Alzheimer's disease (AD); these tangles are bundles of paired helical filaments (PHFs) composed of hyperphosphorylated tau. In particular, phosphorylation at Ser396 by GSK-3 or CDK5 destabilizes microtubules. Furthermore, research studies have shown that inclusions of tau are found in a number of other neurodegenerative diseases, collectively known as tauopathies (1,3).

Alternative splicing of exon 10 results in the expression of two groups of Tau-repeat proteins, the three-repeat tau that expresses microtubule binding domains of isoforms 2, 4, and 5 (Tau 3R), and the four-repeat tau that expresses microtubule-binding domains of isoforms 6, 7, and 8 (Tau 4R) (4). Tau 3R is more abundant in the fetal and postnatal brain compared to Tau 4R, and expresses equal levels compared to Tau 4R (5,6). Tau 3R and 4R are found in aggregates and NFT in Alzheimer's disease brains, whereas other tauopathies selectively express Tau 4R, including in Cortico-Basal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP) (4,7). Tau 3R contributes to the aggregation and NFT formation in tauopathies, including Pick's disease, that develops tau pathology (8,9). A similar pattern occurs in a tauopathy called Frontotemporal Dementia, where Tau 3R and 4R contribute to the pathology, where Tau 3R is slightly elevated compared to Tau 4R (10).