Intracranial administration of deglycosylated C-terminal-specific anti-Aβ antibody efficiently clears amyloid plaques without activating microglia in amyloid-depositing transgenic miceReportar como inadecuado




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Journal of Neuroinflammation

, 3:11

First Online: 10 May 2006Received: 03 January 2006Accepted: 10 May 2006

Abstract

BackgroundAntibodies against the Aß peptide clear Aß deposits when injected intracranially. Deglycosylated antibodies have reduced effector functions compared to their intact counterparts, potentially avoiding immune activation.

MethodsDeglycosylated or intact C-terminal specific high affinity anti-Aβ antibody 2H6 were intracranially injected into the right frontal cortex and hippocampus of amyloid precursor protein APP transgenic mice. The untreated left hemisphere was used to normalize for the extent of amyloid deposition present in each mouse. Control transgenic mice were injected with an antibody against a drosophila-specific protein amnesiac. Tissues were examined for brain amyloid deposition and microglial responses 3 days after the injection.

ResultsThe deglycosylated 2H6 antibody had lower affinity for several murine Fcγ receptors and human complement than intact 2H6 without a change in affinity for Aß. Immunohistochemistry for Aβ and thioflavine-S staining revealed that both diffuse and compact deposits were reduced by both antibodies. In animals treated with the intact 2H6 antibody, a significant increase in Fcγ-receptor II-III immunostaining was observed compared to animals treated with the control IgG antibody. No increase in Fcγ-receptor II-III was found with the deglycosylated 2H6 antibody. Immunostaining for the microglial activation marker CD45 demonstrated a similar trend.

ConclusionThese findings suggest that the deglycosylated 2H6 is capable of removing both compact and diffuse plaques without activating microglia. Thus, antibodies with reduced effector functions may clear amyloid without concomitant immune activation when tested as immunotherapy for Alzheimer-s disease.

Electronic supplementary materialThe online version of this article doi:10.1186-1742-2094-3-11 contains supplementary material, which is available to authorized users.

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







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