People with increased levels of tau protein in their CSF develop late-onset AD at earlier ages than do others with the disease, according to a study by researchers at the Washington University School of Medicine in St. Louis. The levels of this protein in CSF may provide a potential biomarker to identify people who may develop AD sooner than others do. The levels of both beta-amyloid and tau—two proteins whose abnormalities characterize AD—in CSF vary widely in individuals with the disease.
The investigators used genotyping to pinpoint the association between MAPT, the gene that encodes tau, and AD. They found four genetic variants of MAPT that were associated with higher levels of tau, but the higher tau levels were found only in the presence of beta-amyloid deposits. The researchers also confirmed that the genetic variants of MAPT influenced the age at onset of AD clinical symptoms but had no effect on the overall risk of developing AD.
The results indicate that beta-amyloid deposition leads to MAPT gene expression, which in turn raises tau levels and increases early neurodegeneration in late-onset AD.
Kauwe, J.S., et al. Variation of MAPT is associated with cerebrospinal fluid tau levels in the presence of amyloid-beta deposition. Proc Natl Acad Sci USA. 2008 Jun 10. 105(23):8050-54.