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Recent advances in neuroimaging and cerebrospinal fluid (CSF) biomarker assays have provided evidence of a long preclinical stage of Alzheimer’s disease (AD). This period is being increasingly targeted for secondary prevention trials of new therapies. In this context, the interest of a noninvasive, cost-effective amyloid-β (Aβ) blood-based test does not need to be overstated. Nevertheless, a thorough validation of these bioanalytical methods should be performed as a prerequisite for confident interpretation of clinical results. The aim of this study was to validate ELISA sandwich colorimetric ABtest40 and ABtest42 for the quantification of Aβ40 and Aβ42 in human plasma. The validation parameters assessed included precision, accuracy, sensitivity, specificity, recovery, and dilution linearity. ABtest40 and ABtest42 proved to be specific for their target peptide using Aβ peptides with sequence similar to the target. Mean relative error in the quantification was found to be below 7.5% for both assays, with high intra-assay, inter-assay, and inter-batch precision (CV <9.0% on average). Sensitivity was assessed by determination of the limit of quantification fulfilling precision and accuracy criteria; it was established at 7.60 pg/ml and 3.60 pg/ml for ABtest40 and ABtest42, respectively. Plasma dilution linearity was demonstrated in PBS; however, dilution in a proprietary formulated buffer significantly increased the recovery of both Aβ40 and Aβ42 masked by matrix interactions, allowing a more comprehensive assessment of the free and total peptide levels in the plasma. In conclusion, both assays were successfully validated as tools for the quantification Aβ40 and Aβ42 in plasma.

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Dogs may naturally suffer an age-related cognitive impairment that has aroused a great deal of interest, even beyond the field of the veterinary clinic. This canine senile dementia reproduces several key aspects of Alzheimer's disease (AD), including the presence of beta-amyloid (A beta) deposits in the cerebral cortex, neurodegeneration, and learning and memory impairments. In the present study, we have used unbiased stereological procedures to estimate the number of the dorsal and median raphe nuclei (DRN and MRN, respectively) serotonergic neurons immunolabeled with an anti-tryptophan hydroxylase (TrH) monoclonal antibody in young and aged dogs without A beta cortical deposits and in aged dogs with A beta cortical deposits. The estimated total number of TrH-labeled neurons (mean +/- SD) was 94,790 +/- 26,341 for the DRN and 40,404 +/- 8,692 for the MRN. The statistical analyses revealed that aged dogs with A beta cortical pathology had 33% fewer serotonergic neurons in the DRN and MRN than aged dogs without A beta cortical deposits (108,043 +/- 18,800 vs. 162,242 +/- 39,942, respectively; P = 0.01). In contrast, no significant variations were found between young and aged dogs without A beta cortical deposits. These results suggest that degeneration of the serotonergic neurons could be involved in the cognitive damage that accompanies A beta cortical pathology in the dog and reinforce the use of the canine model for exploring the potential mechanisms linking the cortical A beta pathology and serotonergic neurodegeneration that occurs during the course of AD.