Both the inflammatory potential and cognitive function decline during aging. The association between the repertoire of inflammatory biomarkers and cognitive decline is unclear. Inflammatory cytokines have been reported to be increased, decreased, or unchanged in the cerebrospinal fluid and sera of subjects with dementia. We assessed 112 postmortem brains from subjects diagnosed with poststroke dementia (PSD), vascular dementia, mixed dementia, and Alzheimer's disease (AD), comparing those to poststroke nondemented (PSND) subjects and age-matched controls. We analyzed 5 brain regions including the gray and white matter from the frontal and temporal lobes for a panel of cytokine and/or chemokine analytes using multiplex-array assays. Of the 37 analytes, 14 were under or near the detection limits, 7 were close to the lowest detection level, and 16 cytokines were within the linear range of the assay. We observed widely variable concentrations of C-reactive protein (CRP) and serum amyloid A at the high end (1–150 ng/mg protein), whereas several of the interleukins (IL, interferon-gamma and tumor necrosis factor) at the low end (1–10 pg/mg). There were also regional variations; most notable being high concentrations of some cytokines (e.g., CRP and angiogenesis panel) in the frontal white matter. Overall, we found decreased concentrations of several cytokines, including IL-1 beta (p = 0.000), IL-6 (p = 0.000), IL-7 (p = 0.000), IL-8 (p = 0.000), IL-16 (p = 0.001), interferon-inducible protein–10 (0.044), serum amyloid A (p = 0.011), and a trend in IL-1 alpha (p = 0.084) across all dementia groups compared to nondemented controls. IL-6 and IL-8 were significantly lower in dementia subjects than in nondemented subjects in every region. In particular, lower levels of IL-6 and IL-8 were notable in the PSD compared to PSND subjects. Because these 2 stroke groups had comparable degree of vascular pathology, the lower production of IL-6 and IL-8 in PSD reaffirms a possible specific involvement of immunosenescence in dementia pathogenesis. In contrast, CRP was not altered between dementia and nondementia subjects or between PSD and PSND. Our study provides evidence not only for the feasibility of tracking cytokines in postmortem brain tissue but also suggests differentially impaired inflammatory mechanisms underlying dementia including AD. There was a diminished inflammatory response, possibly reflecting immunosenescence and cerebral atrophy, in all dementias. Strategies to enhance anti-inflammatory cytokines and boost the immune system of the brain may be beneficial for preventing cognitive dysfunction, especially after stroke.

Background Blood-based biomarkers for Alzheimer’s disease (AD) are highly needed in clinic practice. So far, the gold standards for AD diagnosis are brain neuroimaging and beta-amyloid peptide, total tau, and phosphorylated tau in cerebrospinal fluid (CSF); however, they are not attractive for large-scale screening. Blood-based biomarkers allow an initial large-scale screening of patients under suspicion that could later be tested for the already established CSF biomarkers. To this regard, in this study, we evaluated whether plasma ADAM10 levels would be predictors of declines in cognition in community-dwelling older adults after a 3-year period follow-up. Methods This was a 3-year longitudinal cohort study that included 219 community-dwelling older adults. Sociodemographic, clinical, lifestyle, depressive symptoms (GDS), and cognitive data (Mini-Mental State Examination, MMSE; Clock Drawing test, CDT) were gathered. The measurement of ADAM10 plasma levels was performed using a sandwich ELISA kit. Bivariate comparisons between groups were performed using Wilcoxon-Mann-Whitney for continuous data and Pearson’s chi-square tests with Yates continuity correction for categorical data. Longitudinal analyzes of changes in the MMSE scores were performed using linear mixed-effects modeling. Results Baseline MMSE scores and ADAM10 levels were significantly associated with MMSE scores on the follow-up assessment. When analyzing the interaction with time, normal MMSE scores and the ADAM10 plasma levels at baseline presented a significant and independent negative association with MMSE score values on the follow-up assessment. The analyses also showed that the predictive effect of ADAM10 plasma levels on decreasing MMSE scores on follow-up seems to be more pronounced in participants with normal MMSE, when compared with those with altered MMSE scores at baseline. Conclusions Considering that ADAM10 increase in plasma is detected as soon as in mild cognitive impairment (MCI) patients, the results presented here may support the complementary clinical use of this biomarker, in addition to the classical AD biomarkers. Taken together, these results provide the first direct evidence that changes in ADAM10 plasma levels are predictors of cognitive worsening in older adults. Moreover, this work can shed light on the study of blood biomarkers for AD and contribute to the advancement of the area.

Background: Blood-based biomarkers for Alzheimer’s disease (AD) are highly needed in clinic practice. So far, the gold standards for AD diagnosis are brain neuroimaging and beta-amyloid peptide, total tau and phosphorylated tau in cerebrospinal fluid (CSF), however, they are not attractive for large-scale screening. Blood-based biomarkers will allow an initial large-scale screening of patients under suspicion that could later be tested for the already established CSF biomarkers. To this regard, we and other research groups have already described that the plasma and platelet levels of ADAM10 are higher or lower, respectively, in patients with AD, compared to those cognitively healthy. Methods: This was a three-year longitudinal cohort study that included 219 community-dwelling older adults. Sociodemographic, clinical, lifestyle, depressive symptoms (GDS) and cognitive data (Mini-Mental State Examination, MMSE; Clock Drawing test, CDT) were gathered. The measurement of ADAM10 plasma levels was performed using a sandwich ELISA kit. Bivariate comparisons between groups were performed using Wilcoxon-Mann-Whitney for continuous data and Pearson’s chi-square tests with Yates continuity correction, for categorical data. Longitudinal analyzes of changes in the MMSE score were performed using Linear Mixed-Effects modeling.Results: Baseline MMSE score and ADAM10 values were significantly associated with MMSE score values on the follow-up assessment. When analyzing the interaction with time, having a normal MMSE at baseline and ADAM10 plasma levels presented a significant and independent negative association with MMSE score values on the follow-up assessment. The analyses also showed that the effect of ADAM10 plasma levels on decreasing MMSE score values on follow-up seems to be more pronounced in those with normal MMSE at baseline. Taken together, these results provide the first direct evidence that changes in ADAM10 plasma levels are predictors of cognitive worsening in older adults.Conclusions: Considering that ADAM10 increase in plasma is detected as soon as in mild cognitive impairment (MCI) patients, the results presented here may support the complementary clinical use of this biomarker, in addition to the classical AD biomarkers. Moreover, this work can shed light on the study of blood biomarkers for AD and contribute to the advancement of the area.