Premium
O2‐03‐04: Utilization of a protease‐generated fragment of tau as a biomarker of Alzheimer's disease
Author(s) -
Sørensen Mette,
Wang Yaguo,
Pajak Monika,
Duffin Kevin,
BayJensen AnneChristine,
Barascuk Natasha,
Karsdal Morten,
Henriksen Kim
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.637
Subject(s) - adam10 , neurodegeneration , tau protein , microbiology and biotechnology , chemistry , alzheimer's disease , monoclonal antibody , human brain , biomarker , recombinant dna , protease , cleavage (geology) , antibody , biochemistry , biology , enzyme , pathology , disease , medicine , immunology , metalloproteinase , neuroscience , disintegrin , gene , paleontology , fracture (geology)
tion, was used as a negative control. Furthermore, we describe a method to abolish interference from human-anti-mouse heterophilic antibodies in human biological samples. Finally, oligomers were measured in CSF samples from AD (n 1⁄4 25) and non-demented control (n 1⁄4 25) patients and brain tissue of both humans (10 AD, 6 controls) and APP/PS1 transgenic mice. Results: First, we showed that oligomers can be measured in biological samples. In transgenic murine tissue, Ab oligomer levels in the cortex and hippocampus increased with age. In human hippocampi, Ab oligomers were significantly increased in AD compared to controls. Ab oligomer levels were similar in CSF of AD and control patients. Characterization of the assay by size-exclusion-chromatography analysis demonstrated that low molecular weight Ab oligomers, rather than larger Ab oligmers, are particularly detected by this ELISA. Conclusions: We developed an ELISA that is specific for low molecular weight Ab oligomers and is able to measure oligomeric Ab in biological samples. Our analysis confirmed that Ab oligomer concentrations are increased in human hippocampal AD tissue compared to controls and increased in Tg mice brain tissue. However CSF concentrations of Ab oligomers, as detected by this assay, may not serve as a biomarker for AD. Future studies will have to reveal if high molecular weight Ab oligomers may serve as such biomarkers.