Correlations between plasma and PET beta-amyloid levels in individuals with subjective cognitive decline: the Fundacio ACE Healthy Brain Initiative (FACEHBI)

BackgroundPeripheral biomarkers that identify individuals at risk of developing Alzheimer's disease (AD) or predicting high amyloid beta (A) brain burden would be highly valuable. To facilitate clinical trials of disease-modifying therapies, plasma concentrations of A species are good candidates for peripheral AD biomarkers, but studies to date have generated conflicting results.MethodsThe Fundacio ACE Healthy Brain Initiative (FACEHBI) study uses a convenience sample of 200 individuals diagnosed with subjective cognitive decline (SCD) at the Fundacio ACE (Barcelona, Spain) who underwent amyloid florbetaben(F-18) (FBB) positron emission tomography (PET) brain imaging. Baseline plasma samples from FACEHBI subjects (aged 65.97.2 years) were analyzed using the ABtest (Araclon Biotech). This test directly determines the free plasma (FP) and total plasma (TP) levels of A40 and A42 peptides. The association between A40 and A42 plasma levels and FBB-PET global standardized uptake value ratio (SUVR) was determined using correlations and linear regression-based methods. The effect of the APOE genotype on plasma A levels and FBB-PET was also assessed. Finally, various models including different combinations of demographics, genetics, and A plasma levels were constructed using logistic regression and area under the receiver operating characteristic curve (AUROC) analyses to evaluate their ability for discriminating which subjects presented brain amyloidosis.ResultsFBB-PET global SUVR correlated weakly but significantly with A42/40 plasma ratios. For TP42/40, this observation persisted after controlling for age and APOE epsilon 4 allele carrier status (R-2=0.193, p=1.01E-09). The ROC curve demonstrated that plasma A measurements are not superior to APOE and age in combination in predicting brain amyloidosis. It is noteworthy that using a simple preselection tool (the TP42/40 ratio with an empirical cut-off value of 0.08) optimizes the sensitivity and reduces the number of individuals subjected to A FBB-PET scanners to 52.8%. No significant dependency was observed between APOE genotype and plasma A measurements (p value for interaction=0.105).Conclusion Brain and plasma A levels are partially correlated in individuals diagnosed with SCD. A plasma measurements, particularly the TP42/40 ratio, could generate a new recruitment strategy independent of the APOE genotype that would improve identification of SCD subjects with brain amyloidosis and reduce the rate of screening failures in preclinical AD studies. Independent replication of these findings is warranted.