Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease
<p>Abstract</p> <p>Background</p> <p>Inflammation is believed to play an important role in the pathology of Alzheimer's disease (AD) and cytokine production is a key pathologic event in the progression of inflammatory cascades. The current study characterizes the c...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2005-03-01
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| Series: | Journal of Neuroinflammation |
| Online Access: | http://www.jneuroinflammation.com/content/2/1/9 |
| _version_ | 1819027362792079360 |
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| author | Quadros Amita N Mathura Venkatarajan Paris Daniel Patel Nikunj S Crawford Fiona C Mullan Michael J |
| author_facet | Quadros Amita N Mathura Venkatarajan Paris Daniel Patel Nikunj S Crawford Fiona C Mullan Michael J |
| author_sort | Quadros Amita N |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Inflammation is believed to play an important role in the pathology of Alzheimer's disease (AD) and cytokine production is a key pathologic event in the progression of inflammatory cascades. The current study characterizes the cytokine expression profile in the brain of two transgenic mouse models of AD (TgAPPsw and PS1/APPsw) and explores the correlations between cytokine production and the level of soluble and insoluble forms of Aβ.</p> <p>Methods</p> <p>Organotypic brain slice cultures from 15-month-old mice (TgAPPsw, PS1/APPsw and control littermates) were established and multiple cytokine levels were analyzed using the Bio-plex multiple cytokine assay system. Soluble and insoluble forms of Aβ were quantified and Aβ-cytokine relationships were analyzed.</p> <p>Results</p> <p>Compared to control littermates, transgenic mice showed a significant increase in the following pro-inflammatory cytokines: TNF-α, IL-6, IL-12p40, IL-1β, IL-1α and GM-CSF. TNF-α, IL-6, IL-1α and GM-CSF showed a sequential increase from control to TgAPPsw to PS1/APPsw suggesting that the amplitude of this cytokine response is dependent on brain Aβ levels, since PS1/APPsw mouse brains accumulate more Aβ than TgAPPsw mouse brains. Quantification of Aβ levels in the same slices showed a wide range of Aβ soluble:insoluble ratio values across TgAPPsw and PS1/APPsw brain slices. Aβ-cytokine correlations revealed significant relationships between Aβ1–40, 1–42 (both soluble and insoluble) and all the above cytokines that changed in the brain slices.</p> <p>Conclusion</p> <p>Our data confirm that the brains of transgenic APPsw and PS1/APPsw mice are under an active inflammatory stress, and that the levels of particular cytokines may be directly related to the amount of soluble and insoluble Aβ present in the brain suggesting that pathological accumulation of Aβ is a key driver of the neuroinflammatory response.</p> |
| first_indexed | 2024-12-21T05:41:16Z |
| format | Article |
| id | doaj.art-fcd0ddac9a904e839355345fffe6d707 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-21T05:41:16Z |
| publishDate | 2005-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-fcd0ddac9a904e839355345fffe6d7072022-12-21T19:14:16ZengBMCJournal of Neuroinflammation1742-20942005-03-0121910.1186/1742-2094-2-9Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's diseaseQuadros Amita NMathura VenkatarajanParis DanielPatel Nikunj SCrawford Fiona CMullan Michael J<p>Abstract</p> <p>Background</p> <p>Inflammation is believed to play an important role in the pathology of Alzheimer's disease (AD) and cytokine production is a key pathologic event in the progression of inflammatory cascades. The current study characterizes the cytokine expression profile in the brain of two transgenic mouse models of AD (TgAPPsw and PS1/APPsw) and explores the correlations between cytokine production and the level of soluble and insoluble forms of Aβ.</p> <p>Methods</p> <p>Organotypic brain slice cultures from 15-month-old mice (TgAPPsw, PS1/APPsw and control littermates) were established and multiple cytokine levels were analyzed using the Bio-plex multiple cytokine assay system. Soluble and insoluble forms of Aβ were quantified and Aβ-cytokine relationships were analyzed.</p> <p>Results</p> <p>Compared to control littermates, transgenic mice showed a significant increase in the following pro-inflammatory cytokines: TNF-α, IL-6, IL-12p40, IL-1β, IL-1α and GM-CSF. TNF-α, IL-6, IL-1α and GM-CSF showed a sequential increase from control to TgAPPsw to PS1/APPsw suggesting that the amplitude of this cytokine response is dependent on brain Aβ levels, since PS1/APPsw mouse brains accumulate more Aβ than TgAPPsw mouse brains. Quantification of Aβ levels in the same slices showed a wide range of Aβ soluble:insoluble ratio values across TgAPPsw and PS1/APPsw brain slices. Aβ-cytokine correlations revealed significant relationships between Aβ1–40, 1–42 (both soluble and insoluble) and all the above cytokines that changed in the brain slices.</p> <p>Conclusion</p> <p>Our data confirm that the brains of transgenic APPsw and PS1/APPsw mice are under an active inflammatory stress, and that the levels of particular cytokines may be directly related to the amount of soluble and insoluble Aβ present in the brain suggesting that pathological accumulation of Aβ is a key driver of the neuroinflammatory response.</p>http://www.jneuroinflammation.com/content/2/1/9 |
| spellingShingle | Quadros Amita N Mathura Venkatarajan Paris Daniel Patel Nikunj S Crawford Fiona C Mullan Michael J Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease Journal of Neuroinflammation |
| title | Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease |
| title_full | Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease |
| title_fullStr | Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease |
| title_full_unstemmed | Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease |
| title_short | Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease |
| title_sort | inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of alzheimer s disease |
| url | http://www.jneuroinflammation.com/content/2/1/9 |
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