Plasma Aß42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study.

BACKGROUND: To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer's disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (Aß) levels with the presence of pathological accumulation of Aß in the brain measured by amyloid-PET. Both plasma Aß42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers. METHODS: We included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total Aß40 and Aß42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as Aß-PET positive or negative, and the ability of TP42/40 to detect Aß-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma Aß biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification. RESULTS: Eighteen (30.5%) subjects were Aß-PET positive. TP42/40 ratio alone identified Aß-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779-0.982). Discriminating performance of TP42/40 to detect Aß-PET-positive subjects yielded sensitivity and specificity values at Youden's cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of Aß-PET scans by 64%. Combination of both FDG-PET scores and plasma Aß biomarkers was found to be the most accurate Aß-PET predictor, with an AUC of 0.965 (95% CI = 0.913-0.100). CONCLUSIONS: Plasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain Aß positivity in preclinical and prodromal stages of Alzheimer's disease.

Host response to Helicobacter pylori infection before initiation of the adaptive immune response.

Helicobacter pylori persistently colonizes the human stomach. In this study, immune responses to H. pylori that occur in the early stages of infection were investigated. Within the first 2 days after orogastric infection of mice with H. pylori, there was a transient infiltration of macrophages and neutrophils into the glandular stomach. By day 10 postinfection, the numbers of macrophages and neutrophils decreased to baseline levels. By 3 weeks postinfection, an adaptive immune response was detected, marked by gastric infiltration of T lymphocytes, macrophages, and neutrophils, as well as increased numbers of H. pylori-specific T cells, macrophages, and dendritic cells in paragastric lymph nodes. Neutrophil-attracting and macrophage-attracting chemokines were expressed at higher levels in the stomachs of H. pylori-infected mice than in the stomachs of uninfected mice. Increased expression of TNFalpha and IFNgamma (Th1-type inflammatory cytokines) and IL-17 (a Th17-type cytokine) was detected in the stomachs of H. pylori-infected mice, but increased expression of IL-4 (a Th2-type cytokine) was not detected. These data indicate that a transient gastric inflammatory response to H. pylori occurs within the first few days after infection, before the priming of T cells and initiation of an adaptive immune response. It is speculated that inappropriate waning of the innate immune response during early stages of infection may be a factor that contributes to H. pylori persistence.