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Background: The over-expression of transforming growth factor β-1(TGF-β1) has been reported to cause hydrocephalus, glia activation, and vascular amyloidβ (Aβ) deposition in mouse brains. Since these phenomena partially mimic the cerebral amyloid angiopathy (CAA) concomitant to Alzheimer's disease, the findings in TGF-β1 over-expressing mice prompted the hypothesis that CAA could be caused or enhanced by the abnormal production of TGF-β1. This idea was in accordance with the view that chronic inflammation contributes to Alzheimer's disease, and drew attention to the therapeutic potential of anti-inflammatory drugs for the treatment of Aβ-elicited CAA. We thus studied the effect of anti-inflammatory drug administration in TGF-β1- induced pathology. Methods: Two-month-old TGF-β1 mice and littermate controls were orally administered pioglitazone, a peroxisome proliferator-activated receptor-γ agonist, or ibuprofen, a non steroidal anti-inflammatory agent, for two months. Glia activation was assessed by immunohistochemistry and western blot analysis; Aβ precursor protein (APP) by western blot analysis; Aβ deposition by immunohistochemistry, thioflavin-S staining and ELISA; and hydrocephalus by measurements of ventricle size on autoradiographies of brain sections. Results are expressed as means ± SD. Data comparisons were carried with the Student's T test when two groups were compared, or ANOVA analysis when more than three groups were analyzed. Results: Animals displayed glia activation, hydrocephalus and a robust thioflavin-S-positive vascular deposition. Unexpectedly, these deposits contained no Aβ or serum amyloid P component, a common constituent of amyloid deposits. The thioflavin-Spositive material thus remains to be identified. Pioglitazone decreased glia activation and basal levels of Aβ42- with no change in APP contents - while it increased hydrocephalus, and had no effect on the thioflavin-S deposits. Ibuprofen mimicked the reduction of glia activation caused by pioglitazone and the lack of effect on the thioflavin-S-labeled deposits. Conclusions: i) TGF-β1 over-expressing mice may not be an appropriate model of Aβ-elicited CAA; and ii) pioglitazone has paradoxical effects on TGF-β1-induced pathology suggesting that anti-inflammatory therapy may reduce the damage resulting from active glia, but not from vascular alterations or hydrocephalus. Identification of the thioflavin-S-positive material will facilitate the full appraisal of the clinical implication of the effects of anti-inflammatory drugs, and provide a more thorough understanding of TGF-β1 actions in brain. [ABSTRACT FROM AUTHOR]