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Comment
. 2006 Nov;116(11):2855-7.
doi: 10.1172/JCI30284.

Dysfunction of TGF-beta signaling in Alzheimer's disease

Pritam Das  1 , Todd Golde
Affiliations
Comment

Dysfunction of TGF-beta signaling in Alzheimer's disease

Pritam Das et al. J Clin Invest. 2006 Nov.

Abstract

Accumulation of beta-amyloid peptide (Abeta) in the brain is believed to trigger a complex and poorly understood pathologic reaction that results in the development of Alzheimer's disease (AD). Despite intensive study, there is no consensus as to how Abeta accumulation causes neurodegeneration in AD. In this issue of the JCI, Tesseur et al. report that the expression of TGF-beta type II receptor (TbetaRII) by neurons is reduced very early in the course of AD and that reduced TGF-beta signaling increased Abeta deposition and neurodegeneration in a mouse model of AD (see the related article beginning on page 3060). Intriguingly, reduced TGF-beta signaling in neuroblastoma cells resulted in neuritic dystrophy and increased levels of secreted Abeta. Collectively, these data suggest that dysfunction of the TGF-beta/TbetaRII signaling axis in the AD brain may accelerate Abeta deposition and neurodegeneration.

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Figures

Figure 1
Figure 1. TGF-β signaling in AD.
Aβ accumulates in the AD brain as amyloid within senile plaques and other smaller, soluble aggregates (oligomers). Aβ plaques are associated with a chronic inflammatory state, including reactive astro- and microgliosis and increased production of numerous inflammatory proteins. Chronic inflammation is hypothesized to induce a complex set of changes in neurons that may ultimately lead to neurodegeneration. The neuroprotective cytokine TGF-β is increased in AD and may reduce deposition of Aβ as plaques while enhancing deposition in the cerebral vessels. In this issue of the JCI, Tesseur et al. (8) show that there is reduced TGF-β signaling in the AD brain, which in turn may promote neuronal degeneration by suppression of neurotrophic factor expression or dysfunction of other unknown neuroprotective pathways. Decreased TGF-β signaling in neurons may also increase Aβ levels, enhancing amyloid deposition. Thus, the inflammatory response to Aβ deposits may initiate a positive feedback loop that exacerbates, rather than ameliorates, AD pathology.
See this image and copyright information in PMC

Comment on

References

    1. Akiyama H., et al. Inflammation and Alzheimer’s disease. Neurobiol. Aging. 2000;21:383–421. - PMC - PubMed
    1. Wyss-Coray T., Mucke L. Inflammation in neurodegenerative disease--a double-edged sword. Neuron. 2002;35:419–432. - PubMed
    1. Glabe C.C. Amyloid accumulation and pathogensis of Alzheimer’s disease: significance of monomeric, oligomeric and fibrillar Abeta. Subcell. Biochem. 2005;38:167–177. - PubMed
    1. Kayed R., et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science. 2003;300:486–489. - PubMed
    1. Walsh D.M., et al. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature. 2002;416:535–539. - PubMed

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