Three-dimensional colocalization analysis of plasma-derived apolipoprotein B with amyloid plaques in APP/PS1...

Parenchymal accumulation of amyloid-beta (A beta) is a hallmark pathological feature of Alzheimer's disease. An emerging hypothesis is that blood-to-brain delivery of A beta may increase with compromised blood-brain barrier integrity. In plasma, substantial A beta is associated with triglyceride-rich lipoproteins (TRLs) secreted by the liver and intestine. Utilizing apolipoprotein B as an exclusive marker of hepatic and intestinal TRLs, here we show utilizing an highly sensitive 3-dimensional immuno-microscopy imaging technique, that in APP/PS1 amyloid transgenic mice, concomitant with substantially increased plasma A beta, there is a significant colocalization of apolipoprotein B with cerebral amyloid plaque. The findings are consistent with the possibility that circulating lipoprotein-A beta contributes to cerebral amyloidosis.