J Neuroinflammation. 2005 Mar
11;2(1):9.
Inflammatory cytokine
levels correlate with amyloid load in transgenic
mouse models of Alzheimer's disease.
Patel NS, Paris D, Mathura V, Quadros AN, Crawford FC, Mullan MJ.
Roskamp Institute,
BACKGROUND: 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 Abeta. METHODS: 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 Abeta
were quantified and Abeta-cytokine relationships were
analyzed. RESULTS: Compared to control littermates, transgenic mice showed a
significant increase in the following pro-inflammatory cytokines: TNF-alpha,
IL-6, IL-12p40, IL-1beta, IL-1alpha and GM-CSF. TNF-alpha, IL-6, IL-1alpha 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 Abeta levels, since PS1/APPsw
mouse brains accumulate more Abeta than TgAPPsw mouse brains. Quantification of Abeta
levels in the same slices showed a wide range of Abeta
soluble:insoluble ratio
values across TgAPPsw and PS1/APPsw brain slices. Abeta-cytokine correlations revealed significant
relationships between Abeta1-40, 1-42 (both soluble and insoluble) and all the
above cytokines that changed in the brain slices. CONCLUSION: 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 Abeta present in the brain suggesting that pathological
accumulation of Abeta is a key driver of the neuroinflammatory response.
Link:
Keywords: Inflammatory, cytokine, amyloid, transgenic mouse, Alzheimer's disease, Journal NeuroInflammation