Transforming growth factor-beta1 (TGF-beta1) has central functions in 
development, tissue maintenance, and repair and has been implicated in major 
diseases. We discovered that TGF-beta1 contains several amphipathic helices and 
hydrophobic domains similar to apolipoprotein E (apoE), a protein involved in 
lipoprotein metabolism. Indeed, TGF-beta1 associates with lipoproteins isolated 
from human plasma, cultured liver cells, or astrocytes, and its bioactivity was 
highest in high-density lipoprotein preparations. Importantly, lipoproteins 
containing the apoE3 isoform had higher TGF-beta levels and bioactivity than 
those containing apoE4, a major genetic risk factor for atherosclerosis and 
Alzheimer's disease. Because TGF-beta1 can be protective in these diseases an 
association with apoE3 may be beneficial. Association of TGF-beta with different 
types of lipoproteins may facilitate its diffusion, regulate signaling, and 
offer additional specificity for this important growth factor.