Relationship between Serum Levels of Tau Fragments and Clinical Progression of Alzheimer's Disease

Article type: Research Article

Authors: Henriksen, Kim^{; *} | Byrjalsen, Inger | Christiansen, Claus | Karsdal, Morten Asser

Affiliations: Nordic Bioscience Biomarkers and Research, Herlev, Denmark

Correspondence: [*] Correspondence to: Kim Henriksen, Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730, Denmark. Tel.: +45 44525219; Fax: +45 44525251; E-mail: kh@nordicbioscience.com.

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.

Keywords: Alzheimer's disease, biomarkers, prediction, serum, tau

DOI: 10.3233/JAD-140984

Journal: Journal of Alzheimer's Disease, vol. 43, no. 4, pp. 1331-1341, 2015