Abstract
Plasma amyloid beta (Aβ) levels are being investigated as potential biomarkers for Alzheimer’s disease. In AB128 cross-sectional study, a number of medical relevant correlates of blood Aβ40 or Aβ42 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 Aβ40 and Aβ42 levels measured in three different blood compartments called i) Aβ directly accessible (DA) in the plasma, ii) Aβ 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 Aβ40 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 Aβ40 levels/DBP correlation are in accordance with previous reports. Of note, DA Aβ40 and the RP Aβ40 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 Aβ levels as potential AD biomarker. Remarkably, the factors affecting Aβ levels in plasma (DA, RP) and blood cell compartments (CP) seem completely different.
Highlights
Alzheimer’s disease (AD) is a global health problem for western countries, representing more than 60% of dementia cases in the world
Beyond the neuropsychological assessment which still represents the most essential tool for AD and mild cognitive impairment (MCI) screening in humans[2], the most reputed biomarkers for AD are cerebral-spinal fluid (CSF) Aβ42 and phosphorylated-tau protein levels, hippocampal volume measured by magnetic resonance imaging (MRI) techniques and positron electronic tomography (PET) scan with brain Aβ radiotracers
Our study indicated that age, creatinine plasma levels and homocysteine were significantly correlated with directly accessible (DA) and RP Aβ 40 levels but not with cell pellet (CP) Aβ 40 or Aβ 42 in any blood compartment
Summary
Alzheimer’s disease (AD) is a global health problem for western countries, representing more than 60% of dementia cases in the world. Beyond the neuropsychological assessment which still represents the most essential tool for AD and mild cognitive impairment (MCI) screening in humans[2], the most reputed biomarkers for AD are cerebral-spinal fluid (CSF) Aβ42 and phosphorylated-tau protein levels, hippocampal volume measured by magnetic resonance imaging (MRI) techniques and positron electronic tomography (PET) scan with brain Aβ radiotracers. These techniques represent the most studied methods for the detection of prodromal AD. Opportunities for diagnosis improvement in prodromal or even pre-symptomatic AD still remain
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