TGFβ1 enhances formation of cellular Aβ/apoE deposits in vascular myocytes

Brain injury increases the risk of Alzheimer’s disease (AD) through unknown mechanisms. We studied deposition of amyloid-β protein (Aβ) in cells exposed to transforming growth factor β1 (TGFβ1), a cytokine that regulates cell metabolism during brain injury, and apolipoproteinE (apoE), the major lipid transporter in the brain. The studies were conducted by using brain vascular smooth muscle cells that are engaged in β-amyloidosis in vivo and produce Aβ in cell culture. We found that cell treatment with TGFβ1 together with apoE4 strongly increased the amount of cellular Aβ. The intracellular Aβ co-localized with apoE but not with TGFβ, similarly as in vascular β-amyloid. Some cellular Aβ/apoE deposits increased in size and persisted in culture even after the TGFβ1 and apoE4 were removed. The appearance of cellular deposits of Aβ was associated with increased production of the amyloid-β precursor protein and cellular retention of its mature form. The results suggest that the concomitant presence of apoE and TGFβ1 can trigger vascular β-amyloidosis by inducing intracellular formation of stable Aβ/apoE deposits.