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Alzheimer-s Research and Therapy

, 9:46

First Online: 27 June 2017Received: 22 February 2017Accepted: 02 June 2017

Abstract

BackgroundFinding ways to reverse or prevent the consequences of pathogenic tau in the brain is of considerable importance for treatment of Alzheimer’s disease and other tauopathies. Immunotherapy against tau has shown promise in several mouse models. In particular, an antibody with selectivity for oligomeric forms of tau, tau oligomer monoclonal antibody TOMA, has shown rescue of the behavioral phenotype in several murine models of tau deposition.

MethodsIn this study, we examined the capacity of TOMA to rescue the behavioral, histological, and neurochemical consequences of tau deposition in the aggressive Tg4510 model. We treated mice biweekly with 60 μg TOMA i.p. from 3.5 to 8 months of age.

ResultsNear the end of the treatment, we found that oligomeric tau was elevated in both the CSF and in plasma. Further, we could detect mouse IgG in Tg4510 mouse brain after TOMA treatment, but not after injection with mouse IgG1 as control. However, we did not find significant reductions in behavioral deficits or tau deposits by either histological or biochemical measurements.

ConclusionsThese data suggest that there is some exposure of the Tg4510 mouse brain to TOMA, but it was inadequate to affect the phenotype in these mice at the doses used. These data are consistent with other observations that the rapidly depositing Tg4510 mouse is a challenging model in which to demonstrate efficacy of tau-lowering treatments compared to some other preclinical models of tau deposition-overexpression.

KeywordsTau Immunotherapy Tg4510 mouse Oligomers AbbreviationsACXAnterior cortex

ADAlzheimer’s disease

CSFCerebrospinal fluid

HPCHippocampus

nTgNontransgenic

PCXPosterior cortex

TetTetracycline response element transgenic

TOMATau oligomer monoclonal antibody

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Autor: Sulana Schroeder - Aurelie Joly-Amado - Ahlam Soliman - Urmi Sengupta - Rakiz Kayed - Marcia N. Gordon - David Morgan

Fuente: https://link.springer.com/







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