Detecting tau in serum of transgenic animal models after tau immunotherapy treatment.
In the attempt to elucidate if the "peripheral sink hypothesis" could be a potential mechanism of action for tau removal in passive immunotherapy experiments, we have examined tau levels in serum of chronically injected JNPL3 and Tg4510 transgenic animals. Measurement of tau in serum of mice treated with tau antibodies is challenging because of the antibody interference in sandwich enzyme-linked immunosorbent assays. To address this issue, we have developed a heat-treatment protocol at acidic pH to remove interfering molecules from serum, with excellent recovery of tau. The present data show that pan-tau and conformational antibodies do increase tau in mouse sera. However, these concentrations in serum do not consistently correlate with reductions of tau pathology in brain, suggesting that large elevations of tau species measured in serum are not predictive of efficacy. Here, we describe a reliable method to detect tau in serum of transgenic animals that have undergone tau immunotherapy. Levels of tau in human serum are less than the sensitivity of current assays, although artifactual signals are common. The method may be useful in similarly treated humans, a situation in which false positive signals are likely.
Litwin-Zucker Center for Research in Alzheimer's Disease, Feinstein Institute for Medical Research, North Shore/LIJ Health System, Manhasset, NY, USA.
Cristina
C
d'Abramo
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
Christopher M
CM
Acker
Department of Neuroscience, Merck Research Laboratories, West Point, PA, USA.
Joel B
JB
Schachter
Department of Pharmacology Merck Research Laboratories, Kenilworth, NJ, USA.
Giuseppe
G
Terracina
Department of Neuroscience, Merck Research Laboratories, West Point, PA, USA.
Xiaohai
X
Wang
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
Stefanie K
SK
Forest
Litwin-Zucker Center for Research in Alzheimer's Disease, Feinstein Institute for Medical Research, North Shore/LIJ Health System, Manhasset, NY, USA. Electronic address: pdavies@nshs.edu.
Peter
P
Davies
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007116:Immunization, Passive / Q000379:methods*; D008822:Mice, Transgenic; D011237:Predictive Value of Tests; D024801:Tauopathies / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D016875:tau Proteins / Q000097:blood* / Q000276:immunology* / Q000302:isolation & purification
D000906:Antibodies; D015415:Biomarkers; D016875:tau Proteins
Extracellular tau; Human antibodies against mouse immunoglobulin; Tau ELISA; Tau immunotherapy; Tau in serum