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

Plasma amyloid beta (A beta) levels are being investigated as potential biomarkers for Alzheimer's disease. In AB128 cross-sectional study, a number of medical relevant correlates of blood A beta 40 or A beta 42 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 A beta 40 and A beta 42 levels measured in three different blood compartments called i) A beta directly accessible (DA) in the plasma, ii) A beta 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 A beta 40 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 A beta 40 levels/DBP correlation are in accordance with previous reports. Of note, DA A beta 40 and the RP A beta 40 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 A beta levels as potential AD biomarker. Remarkably, the factors affecting A beta levels in plasma (DA, RP) and blood cell compartments (CP) seem completely different.