Sylvain Lesné and colleagues, working with Denis Vivien at the Université de Caen, France, found that transgenic mice overexpressing transforming growth factor β-1 (TGFβ-1) also have increased transcription of AβPP and twice as much Aβ and Aβ in the brain as do control animals. To find out where this extra protein is coming from, Lesné and colleagues treated cultured cells with TGF-β. While neuronal AβPP levels remained unchanged, AβPP expression in astrocytes increased. The authors found that the AβPP gene harbors a TGF-β response element, which is required for the effect of the cytokine, suggesting that TGF-β acts directly on the cells.

Lesné and coworkers found that cultured human astrocytes also respond to TGF-β by upregulating production of AβPP. This, plus the fact that Alzheimer's patients have higher levels of the cytokine in the brain than do control subjects (see ARF related news story), and the finding of TGF-β in amyloid plaques (see van der Wal et al., 1993), suggest that the cytokine may play a role in amyloidogenesis.—Tom Fagan.

Reference:
Lesne S, Docagne F, Gabriel C, Liot G, Lahiri DK, Buee L, Plawinski L, Delacourte A, MacKenzie ER, Buisson A, Vivien D. TGF-beta1 potentiates amyloid-beta generation in astrocytes and in transgenic mice. J Biol Chem. 2003 Mar 7. Abstract