Blood amyloid beta levels in healthy, mild cognitive impairment and Alzheimer's disease individuals: replication of diastolic blood pressure correlations and analysis of critical covariates.

ABSTRACT

Plasma amyloid beta (Aß) levels are being investigated as potential biomarkers for Alzheimer's disease. In AB128 cross-sectional study, a number of medical relevant correlates of blood Aß40 or Aß42 were analyzed in 140 subjects (51 Alzheimer's disease patients, 53 healthy controls and 36 individuals diagnosed with mild cognitive impairment). We determined the association between multiple variables with Aß40 and Aß42 levels measured in three different blood compartments called i) Aß directly accessible (DA) in the plasma, ii) Aß recovered from the plasma matrix (RP) after diluting the plasma sample in a formulated buffer, and iii) associated with the remaining cellular pellet (CP). We confirmed that diastolic blood pressure (DBP) is consistently correlated with blood DA Aß40 levels (r=-0.19, P=0.032). These results were consistent in the three phenotypic groups studied. Importantly, the observation resisted covariation with age, gender or creatinine levels. Observed effect size and direction of Aß40 levels/DBP correlation are in accordance with previous reports. Of note, DA Aß40 and the RP Aß40 were also strongly associated with creatinine levels (r=0.599, P<<0.001) and to a lesser extent to urea, age, hematocrit, uric acid and homocysteine (p<0.001). DBP and the rest of statistical significant correlates identified should be considered as potential confounder factors in studies investigating blood Aß levels as potential AD biomarker. Remarkably, the factors affecting Aß levels in plasma (DA, RP) and blood cell compartments (CP) seem completely different.