Oct 30, 2012

Extracellular Tau levels are influenced by variability in Tau that is associated with tauopathies

The Journal of Biological Chemistry
Celeste M KarchAlison M Goate

Abstract

Tauopathies are a class of neurodegenerative diseases marked by intracellular aggregates of hyperphosphorylated Tau. These diseases may occur by sporadic mechanisms in which genetic variants represent risk factors for disease, as is the case in Alzheimer disease (AD). In AD, cerebrospinal fluid (CSF) levels of soluble Tau/pTau-181 are higher in cases compared with controls. A subset of frontotemporal dementia (FTD) cases occur by a familial mechanism in which MAPT, the gene that encodes Tau, mutations are dominantly inherited. In symptomatic FTD patients expressing a MAPT mutation, CSF Tau levels are slightly elevated but are significantly lower than in AD patients. We sought to model CSF Tau changes by measuring extracellular Tau in cultured cells. Full-length, monomeric extracellular total Tau and pTau-181 were detectable in human neuroblastoma cells expressing endogenous Tau, in human non-neuronal cells overexpressing wild-type Tau, and in mouse cortical neurons. Tau isoforms influence the rate of Tau release, whereby the N terminus (exons 2/3) and microtubule binding repeat length contribute to Tau release from the cell. Compared with cells overexpressing wild-type Tau, cells overexpressing FTD-associated MAPT mutations pro...Continue Reading

  • References63
  • Citations48

References

Mentioned in this Paper

Tauopathies
HEK293 Cells
Central Neuroblastoma
Exons
Extracellular
Secretory Pathway
Protoplasm
Neurons
Extracellular Space
Cerebrospinal Fluid

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