Introduction Relationship between self– and informant memory concerns and tau aggregation was assessed in adults at risk for Alzheimer's disease (AD). Methods Regional mean standardized uptake value ratios were extracted from [ 18 F]flortaucipir positron emission tomography (PET) scans of 82 at-risk adults in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Associations between self– and informant ECog memory scores and tau aggregation were analyzed on both regional and voxelwise bases. Analyses were completed both on the whole sample and restricted to amyloid-positive individuals only. Results Memory concerns were associated with tau aggregation. Self-perception was more associated with frontal tau. In contrast, informant scores were more associated with parietal tau. This source-by-region interaction was more prominent in amyloid-positive participants and observed in both regional and voxelwise analyses. Discussion Quantitative assessment of perceived memory functioning may be useful for screening older adults at risk for Alzheimer's disease. Individuals and their informants may provide complementary information relating to the anatomical distribution of tau.

Background: Aberrant angiogenesis may play a role in the development of Alzheimer's disease and related dementia. Objective: To explore the relationship between angiogenesis activity and evidence of neurodegeneration among older adults. Methods: Cross-sectional study of 49 older adults clinically characterized as cognitively normal, mild cognitive impairment, or early Alzheimer's disease. In addition to neuroimaging, we completed assays on peripheral blood, including: vascular endothelial growth factor, tumor necrosis factor, fibroblast growth factor, and amyloid-␤ peptide 40. We used advanced polychromatic flow cytometry to phenotype circulating mononuclear cells to assess angiogenesis activity. Results: Although we documented differences in cognitive performance, structural changes on neuroimaging, and burden of amyloid and tau on positron emission tomography, angiogenesis activity did not vary by group. Interestingly, VEGF levels were shown to be increased among subjects with mild cognitive impairment. In ANCOVA models controlling for age, sex, intracranial volume, and monocyte subpopulations, angiogenesis activity was correlated with increased white matter hyperintensities. Conclusion:We demonstrate a significant association between angiogenesis activity and cerebrovascular disease. To better understand the potential of angiogenesis as an intervention target, longitudinal studies are needed.

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Periodontitis-a biofilminduced immunoinflammatory pathology-often progresses gradually, exhibiting periodic bursts and resolution. Exfoliating oral epithelial cells act as reservoirs for key periodontal pathogens, facilitating reinfection or infection of new sites. Since saliva is a rich source of oral epithelial cells, we hypothesized that the microbial and functional profile of salivary epithelial cells (SECs) will reflect the in situ host response and disease severity. We used a casecontrol study design. Unstimulated whole saliva was collected from 20 chronic periodontitis patients and 20 healthy controls in accordance with the institutional review board. The isolated SECs were assessed for viability by trypan blue exclusion. Gram-stained SECs were analyzed by ImageJ, and Gram stain index (GSI) per SEC was calculated. Equal numbers of SECs from each sample were exposed to 2 periodontal pathogens-Porphyromonas gingivalis and Fusobacterium nucleatum-in biofilm or planktonic formulations at varying proportions. Cytokines in culture supernatants were assessed by ELISA (enzyme-linked immunosorbent assay). Additionally, soluble Tolllike receptor 2 (sTLR-2)-a pattern recognition receptor capable of binding microbial ligands associated with periodontitis-was measured in clarified saliva by ELISA. An increased number of SECs, a higher GSI/SEC, and a lower sTLR-2 were observed in periodontitis saliva as compared with healthy saliva. SECs from periodontitis saliva secreted higher amounts of interleukin 8 in response to P. gingivalis, and the presence of F. nucleatum dampened the response. Nonsurgical periodontal treatment improved clinical parameters, reduced the number of SECs, decreased GSI/ SEC, and increased sTLR-2 in clarified saliva. In conclusion, our data suggest that SECs can provide a phenotypically distinct individualized resource for assessing epithelial response to pathogens in the course of periodontal disease. Furthermore, correlation between the sTLR-2 and GSI/SEC suggests that the expression profile of epithelial and soluble Toll-like receptor could provide an indirect measure of periodontal disease-associated dysbiosis. Knowledge Transfer Statement: The results of this study can be used for prognostic evaluation of chronic periodontitis in response to therapy and provide an opportunity for early identification of poor responders. A chip-based simple test incorporating the identified salivary epithelial cell characteristics can be developed and validated for future clinical applications, especially for monitoring patients with increased susceptibility for refractory and/or recurrent periodontitis.

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