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 journalArticle

67 Citations (Scopus)

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

Fingerprint

Amyloid
Tumor Necrosis Factor-alpha
Pathology
Cytokines
Transgenic Mice
Alzheimer Disease
Dependovirus
Brain Diseases
Neuroglia
Hippocampus
Peptides

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Clinical Neurology
  • Molecular Biology

Cite this

Hippocampal expression of murine TNF results in attenuation of amyloid deposition in vivo. / Chakrabarty, Paramita; Herring, Amanda; Ceballos-Diaz, Carolina; Das, Pritam; Golde, Todd E.

In: Molecular Neurodegeneration, Vol. 6, No. 1, 16, 2011.

Research output: Contribution to journalArticle

Chakrabarty, Paramita ; Herring, Amanda ; Ceballos-Diaz, Carolina ; Das, Pritam ; Golde, Todd E. / Hippocampal expression of murine TNF results in attenuation of amyloid deposition in vivo. In: Molecular Neurodegeneration. 2011 ; Vol. 6, No. 1.
@article{3903819f9eb64f5696a6072c7aed6d82,
title = "Hippocampal expression of murine TNF results in attenuation of amyloid deposition in vivo",
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.",
author = "Paramita Chakrabarty and Amanda Herring and Carolina Ceballos-Diaz and Pritam Das and Golde, {Todd E.}",
year = "2011",
doi = "10.1186/1750-1326-6-16",
language = "English (US)",
volume = "6",
journal = "Molecular Neurodegeneration",
issn = "1750-1326",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Hippocampal expression of murine TNF results in attenuation of amyloid deposition in vivo

AU - Chakrabarty, Paramita

AU - Herring, Amanda

AU - Ceballos-Diaz, Carolina

AU - Das, Pritam

AU - Golde, Todd E.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79951551206&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951551206&partnerID=8YFLogxK

U2 - 10.1186/1750-1326-6-16

DO - 10.1186/1750-1326-6-16

M3 - Article

C2 - 21324189

AN - SCOPUS:79951551206

VL - 6

JO - Molecular Neurodegeneration

JF - Molecular Neurodegeneration

SN - 1750-1326

IS - 1

M1 - 16

ER -