Tau, pTau and MTBR-tau biomarkers in Alzheimer’s Disease and other tauopathies

Chihiro Sato, Nicolas R. Barthelemy, Kanta Horie, Randall J. Bateman

Department of Neurology, Washington University School of Medicine

Recent studies by us and others suggest that in both cerebrospinal fluid （CSF） and blood, phosphorylated tau （ptau） at T217 （pT217） strongly correlate with amyloid pathology and outperforms the classic ptau biomarker used in research and clinic, pT181, as a biomarker of Alzheimer’s disease （AD）.　This led to our ongoing and recent efforts to further identify tau species that contributes to or results from pathogenesis of AD.　In our laboratory, we utilize immunoprecipitation and quantitative mass spectrometry to capture the heterogeneity of tau, including phosphorylation at multiple sites, truncations and isoforms.　In autosomal dominant AD mutation carriers, CSF ptau at different sites （i.e. pT181, pT205, pT217） were shown to increase at different stages of disease.　CSF tau is truncated at mid domain and primarily exists as a N-terminus stub, but we have recently identified complementary C-terminus stub containing Microtubule Binding Region （MTBR）, which we call MTBR-tau.　We found that MTBR-tau is a new AD biomarker and correlates with tau pathology and associates with different stages of AD and other tauopathies.　This review will summarize different species of tau, ptau and MTBR-tau and their sensitivity and specificity as AD biomarkers.　We will also show that CSF pT217 is increased in MAPT R406W mutation carriers without amyloid pathology, suggesting that pT217 is not specific to AD.

Address correspondence to Dr. Chihiro Sato, Department of Neurology, Washington University School of Medicine （660 S Euclid Ave #8111 St.Louis, MO 63110 USA）