What is the role of tau protein in the pathophysiology of progressive supranuclear palsy (PSP)?

Updated: Sep 24, 2018
  • Author: Stephen M Bloomfield, MD; Chief Editor: Selim R Benbadis, MD  more...
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Answer

PSP has been considered to be a tau protein disorder. [21] Cortical fibrillary tangles of PSP are similar to those observed in Alzheimer disease with regard to the presence of an abnormally phosphorylated tau protein. Tau is a component of a microtubule-associated protein that is responsible for axonal transport of vesicles. The mechanism whereby this is involved in PSP has yet to be determined. PSP overlaps with corticobasal degeneration (CBD) in this regard, and the latter may have a stronger association with tau protein abnormalities than does PSP.

Tau proteins exist in 6 isoforms encoded by a single gene. Different electrophoretic patterns have been identified in the various disorders associated with tau abnormalities. Thirty-two mutations have been identified in more than 100 families. [22] About half of the known mutations have their primary effect at the protein level. They reduce the ability of tau protein to interact with microtubules and increase its propensity to assemble into abnormal filaments. The other mutations have their primary effect at the RNA level and perturb the normal ratio of 3-repeat to 4-repeat tau isoforms. When studied, this change resulted in a relative overproduction of tau protein with 4 microtubule-binding domains in the brain.

In Alzheimer disease, the pattern consists of a paired helical fragment triplet (55/64/69), whereas in PSP and CBGD, a tau doublet (64/69) is observed. In Pick disease, a different tau doublet (55/64) is observed. Tau protein abnormalities also have been found in frontotemporal dementia, with parkinsonism linked to chromosome 17 (FTDP-17). The chromosomal region containing MAPT has been shown to evolve into 2 major haplotypes, H1 and H2. The more common haplotype, H1, is overrepresented in patients with PSP and CBD. A study of these abnormalities promises further insights into the pathogenesis of these diseases. However, clinical applications are limited at this time.


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