Pathology: taupathies

In different neurological disorders, known as taupathies, modifications in the microtubule-associated protein tau could cause neural degeneration in specific regions. These 'taupathies' are due to Tau aggregation into fibrillar polymers.

Although these regions are different in the different taupathies, some common features appear to occur in all of them: abnormal hyperphosphorylation of tau and aberrant tau aggregation. These two features are commented upon in this review.

 mutations in familial cases of frontotemporal dementia. The mutations reduce the ability of tau to promote microtubule assembly. The different tau mutations may result in disturbances in the interactions of the protein tau with microtubules, resulting in hyperphosphorylation of tau protein, assembly into filaments, and subsequent cell death.

Tau protein aggregation (Abundant cytoplasmic inclusions consisting of aggregated hyperphosphorylated protein tau)

 Alzheimer's disease
 Pick's disease
 frontotemporal dementia
 cortico-basal degeneration
 progressive supranuclear palsy

Features

 the Ras/MEK/ERK pathway of tau phosphorylation
 tau polymerization

References

 Yancopoulou D, Spillantini MG. Tau protein in familial and sporadic diseases. Neuromolecular Med. 2003;4(1-2):37-48. PMID: #14528051#

 Ingram EM, Spillantini MG. Tau gene mutations: dissecting the pathogenesis of FTDP-17. Trends Mol Med. 2002 Dec;8(12):555-62. PMID: #12470988#

 Heutink P. Untangling tau-related dementia. Hum Mol Genet. 2000 Apr 12;9(6):979-86. PMID: #10767321#

 Grundke-Iqbal I, Iqbal K. Tau pathology generated by overexpression of tau. Am J Pathol. 1999 Dec;155(6):1781-5. PMID: #10595905#