title: Relationship between serum levels of tau fragments and clinical progression of Alzheimer's disease.
abstract: Enzyme-generated fragments of tau have been linked to neuronal death and may serve as serum biomarkers of cognitive loss. Two competitive ELISAs detecting an ADAM10-generated fragment (Tau-A) or a caspase-3-generated fragment (Tau-C) were measured in baseline serum samples from patients with mild to moderate Alzheimer's disease (AD) from a Phase III clinical trial, and correlated to change in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog11) and Clinical Dementia Rating-Sum of Boxes (CDR-SB) over a 64-week period using an MMRM-analysis. Relationship between the biomarkers and changes in ADAS-Cog11 score as a function of time were observed for Tau-C and change in ADAS-Cog11 (p = 0.06), and for Tau-A and change in CDR-SB (p = 0.04). The correlation of Tau-A/Tau-C ratio with cognitive change assessed by ADAS-Cog11 was even more significant (p < 0.006). These data indicate that measuring the balance between tau fragments in serum may provide a marker of the rate of progression of AD and warrant studies in larger cohorts.
authors.affiliation: Nordic Bioscience Biomarkers and Research, Herlev, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Henriksen
authors.affiliation: Nordic Bioscience Biomarkers and Research, Herlev, Denmark.
authors.forename: Inger
authors.initials: I
authors.lastname: Byrjalsen
authors.affiliation: Nordic Bioscience Biomarkers and Research, Herlev, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.affiliation: Nordic Bioscience Biomarkers and Research, Herlev, Denmark.
authors.forename: Morten Asser
authors.initials: MA
authors.lastname: Karsdal
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008609:Mental Status Schedule; D012720:Severity of Illness Index; D013997:Time Factors; D016875:tau Proteins / Q000097:blood*
chemical_list: D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins
keywords: Alzheimer's disease; biomarkers; prediction; serum; tau