Association between cell-bound blood amyloid-β(1-40) levels and hippocampus volume

Introduction: The identification of early, preferably presymptomatic, biomarkers and true etiologic factors fo Alzheimer's disease (AD) is the first step toward establishing effective primary and secondary prevention programs Consequently, the search for a relatively inexpensive and harmless biomarker for AD continues. Despite intensiv research worldwide, to date there is no definitive plasma or blood biomarker indicating high or low risk o conversion to AD Methods: Magnetic resonance imaging and β-Amyloid (Aβ) levels in three blood compartments (diluted in plasma undiluted in plasma and cell-bound) were measured in 96 subjects (33 with mild cognitive impairment, 14 with A and 49 healthy controls). Pearson correlations were completed between 113 regions of interest (ROIs) (45 subcortica and 68 cortical) and Aβ levels. Pearson correlation analyses adjusted for the covariates age, sex, apolipoprotein E (ApoE) education and creatinine levels showed neuroimaging ROIs were associated with Aβ levels. Two statistical method were applied to study the major relationships identified: (1) Pearson correlation with phenotype added as a covariat and (2) a meta-Analysis stratified by phenotype. Neuroimaging data and plasma Aβ measurements were taken fro 630 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects to be compared with our results Results: The left hippocampus was the brain region most correlated with Aβ(1-40) bound to blood cell pellet (partial correlation (pcor) = ?0.37, P = 0.0007) after adjustment for the covariates age, gender and education, Apo and creatinine levels. The correlation remained almost the same (pcor = ?0.35, P = 0.002) if phenotype is als added as a covariate. The association between both measurements was independent of cognitive status. The lef hemisphere entorhinal cortex also correlated with Aβ(1-40) cell-bound fraction. AB128 and ADNI plasma A measurements were not related to any brain morphometric measurement Conclusions: Association of cell-bound Aβ(1-40) in blood with left hippocampal volume was much stronger tha previously observed in Aβ plasma fractions. If confirmed, this observation will require careful interpretation an must be taken into account for blood amyloid-based biomarker development.