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TAU (MAPT, 17q21.1)

The size of the tau gene can vary from ∼352 to 441 amino acids in the isoforms of the microtubule-associated proteins by alternative splicing of the mRNA (Margittai M, Langen R 2004 Proc Natl Acad Sci USA 101:10278).

By reducing motor reattachment rates, tau affects cargo travel distance, motive force, and cargo dispersal. Different isoforms of tau, at concentrations similar to those in cells, have dramatically different potency.

These defined mechanism show how altered tau isoform levels could impair transport and thereby lead to neurodegeneration without the need of any other pathway (Vershinin M et al 2007 Proc Natl Acad Sci USA 104:87). It seems to form tangles by virtue of the 306Val-Gln-Ile-Val-Tyr-Lys311 motif in the 6 tau monomers in several types of nerve degenerative diseases (e.g., Pick disease, Alzheimer disease, progressive supranuclear palsy, corticobasal degeneration).

A pseudogene exists at 6q21. Base substitution and splice site mutations may