Association between cell bound blood beta-amyloid 1-40 levels and hippocampus volume.


The identification of early, preferably pre-symptomatic, biomarkers and true etiologic factors for Alzheimer’s disease (AD) is the first step to establish effective primary and secondary prevention programs. Consequently, the search for a relatively inexpensive and harmless biomarker for AD continues. Despite intensive research worldwide, to date, there is no definitive plasma or blood biomarker indicating high/low risk of conversion to AD.
Magnetic resonance imaging (MRI) and β-amyloid (Aβ) levels in three blood compartments (diluted in plasma, undiluted in plasma and cell bound) were measured in 96 subjects (33 mild cognitive impairment (MCI), 14 AD, 49 healthy controls (HC)). Pearson correlations were completed between 113 regions of interest (ROI) (45 subcortical and 68 cortical) and Aβ levels. Pearson correlation analyses adjusted by covariates apolipoprotein E (APOE), age, sex and creatinine variables showed neuroimaging ROIs associated to Aβ levels. Two statistical methods were applied to study the major relationships identified: i) Pearson correlation adding also phenotype as a covariate and ii) a meta-analysis stratified by phenotype. Neuroimaging data and plasma Aβ measurements were taken from 630 Alzheimer’s Disease Neuroimaging Initiative (ADNI) subjects to be compared with our results.
Left hippocampus volume was the brain region most correlated with Aβ1-40 bound to blood cell pellets (pcor = -0.37, p-value = 0.0007) after adjustment by 4 the covariates: age, gender, education, APOE and creatinine. The correlation remained almost the same (pcor = -0.35, p-value = 0.002) if phenotype is also added as a covariate. The association between both measurements was independent of cognitive status. Left hemisphere entorhinal cortex also correlated with Aβ1-40 cell bound fraction. AB128 and ADNI plasma Aβ measurements were not related to any brain morphometric measurement.
Association of cell-bound Aβ1-40 in blood with left hippocampus volume was much stronger than previously observed in Aβ plasma fractions. If confirmed, this observation will require careful interpretation and must be taken into account for blood amyloid-based biomarker development.

Referencia: Alzheimer's Research & Therapy