TAU-C, A CASPASE-3 CLEAVED FRAGMENT OF TAU: A SERUM BIOMARKER FOR PRECLINICAL DEMENTIA

Abstract

There is a clear need for non-invasive and reliable biomarkers to aid in early prognosis, diagnosis and early efficacy assessment for dementia disorders. The caspase-3-generated fragment of tau (Tau-C), incorporating the Asp421 site, is considered a key player in the filament formation eventually leading to tangle formation (Rissman et al. 2004). The aim of this study was to investigate this particular pathological protein fragment in serum, in a large prospective cohort of elderly women who has been followed for up to 15 years. Using competitive ELISA, Tau-C was measured in baseline serum samples from subjects in the Prospective Epidemiological Risk Factor (PERF) Study (n=5,632). The subjects were stratified in three groups; dementia free controls (n=5,005), subjects with established dementia (n=15), and subjects later diagnosed with dementia (n=612). The levels of Tau-C were compared using Kruskal-Wallis test. The prognostic utility in combination with baseline cognitive performance, was assessed in relation to risk of dementia using Cox regression. Tau-C levels were dichotomized using the median. The cognitive test was the Short Blessed Test. Our data suggest that Tau-C could have prognostic utility as an early marker for dementia. The increased risk of dementia for subjects with low levels of Tau-C and normal cognition could reflect the accumulation of caspase-cleaved Tau in neuronal cells in an early disease stage. Opposite, the possible increased risk for subjects with high Tau-C levels and severe impairment could indicate that these subjects are actually in a diseased stage, where dying neurons release caspase-cleaved tau into the surroundings.