Hippocampal expression of murine TNF results in attenuation of amyloid deposition in vivo

Paramita Chakrabarty, Amanda Herring, Carolina Ceballos-Diaz, Pritam Das, Todd E. Golde

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Fibrillar amyloid (fA) peptide is the major component of A plaques in the brains of Alzheimer's disease (AD) patients. Inflammatory mediators have previously been proposed to be drivers of A pathology in AD patients by increasing amyloidogenic processing of APP and promoting A accumulation, but recent data have shown that expression of various inflammatory cytokines attenuates A pathology in mouse models. In an effort to further study the role of different inflammatory cytokines on A pathology in vivo, we explored the effect of murine Tumor Necrosis Factor (mTNF) in regulating A accumulation. Recombinant adeno-associated virus serotype 1 (AAV2/1) mediated expression of mTNF in the hippocampus of 4 month old APP transgenic TgCRND8 mice resulted in significant reduction in hippocampal A burden. No changes in APP levels or APP processing were observed in either mTNF expressing APP transgenic mice or in non-transgenic littermates. Analysis of A plaque burden in mTNF expressing mice showed that even after substantial reduction compared to EGFP expressing age-matched controls, the A plaque burden levels of the former do not decrease to the levels of 4 month old unmanipulated mice. Taken together, our data suggests that proinflammatory cytokine expression induced robust glial activation can attenuate plaque deposition. Whether such an enhanced microglial response actually clears preexisting deposits without causing bystander neurotoxicity remains an open question.

Original languageEnglish (US)
Article number16
JournalMolecular neurodegeneration
Volume6
Issue number1
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Hippocampal expression of murine TNF results in attenuation of amyloid deposition in vivo'. Together they form a unique fingerprint.

Cite this