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The semi-quantitative estimate standardised uptake value ratios (SUVR) correlate well with specific binding of the tracer expressed as distribution volume ratios (DVR) for the tau positron emission tomography tracer [ 18 F]AV-1451 uptake and are therefore widely used as proxy for tracer binding. With regard to tracer kinetic modelling, there exists a time point when SUVR deviates minimally from DVR, occurring when the specific binding reaches a transient equilibrium . Here, we have investigated whether the time to equilibrium affects the agreement between SUVR and DVR across different brain regions. We show that the time required to reach equilibrium differs across brain regions, resulting in region-specific biases. However, even though the 80-100 min post-injection time window did not show the smallest bias numerically, the disagreement between SUVR and DVR varied least between regions during this time. In conclusion, our findings suggest a regional component to the bias of SUVR related to the time to transient equilibrium of the specific binding. [ 18 F]AV-1451 uptake should consequently be interpreted with some caution when compared across brain regions using this method of quantification. The commonly used time window 80-100 min post-injection shows the most consistent bias across regions and is recommended for semi-quantification of [ 18 F]AV-1451.

Changes in P-glycoprotein and ABCG2 densities may play a role in amyloid-beta accumulation in Alzheimer's disease. However, previous studies report conflicting results from different brain regions, without correcting for changes in vessel density. We developed an automated method to measure transporter density exclusively within the vascular space, thereby correcting for vessel density. We then examined variability in transporter density across brain regions, matter, and disease using two cohorts of post-mortem brains from Alzheimer's disease patients and age-matched controls. Changes in transporter density were also investigated in capillaries near plaques and on the mRNA level. P-glycoprotein density varied with brain region and matter, whereas ABCG2 density varied with brain matter. In temporal cortex, P-glycoprotein density was 53% lower in Alzheimer's disease samples than in controls, and was reduced by 35% in capillaries near plaque deposits within Alzheimer's disease samples. ABCG2 density was unaffected in Alzheimer's disease. No differences were detected at the transcript level. Our study indicates that region-specific changes in transporter densities can occur globally and locally near amyloid-beta deposits in Alzheimer's disease, providing an explanation for conflicting results in the literature. When differences in region and matter are accounted for, changes in density can be reproducibly measured using our automated method.