Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome

Background: Basal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS. Methods: We included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume. Results: In DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance. Discussion: BF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS

GM-CSF inhibits c-kit and SCF expression by Dendritic Cells

Stem Cell Factor (SCF), the ligand of c-kit, is a key cytokine for hematopoiesis. Hematopoietic precursors express c-kit, whereas differentiated cells of hematopoietic lineage are negative for this receptor, with the exception of NK cells, mast cells and a few others. While it has long been recognized that dendritic cells (DCs) can express c-kit, several questions remain concerning the SCF/c-kit axis in DCs. This is particularly relevant for DCs found in those organs wherein SCF is highly expressed, including the bone marrow (BM). We characterized c-kit expression by cDCs from BM, and demonstrated a higher proportion of c-kit+ cells among cDC1s than cDC2s in both humans and mice, whereas similar levels of c-kit expression were observed in cDC1s and cDC2s from mouse spleen. To further study c-kit regulation, mouse BM-derived DCs (BMdDCs) were generated with GM-CSF, a widely used protocol. BMdDCs contained a small fraction of c-kit+ cells, and by re-plating them for 2 days with GM-CSF we obtained a homogeneous population of c-kit+ CD40hi MHCIIhi cells. Not only did BMdDCs express c-kit, but they also produced SCF, and both were striking up-regulated if GM-CSF was omitted after re-plating. Furthermore, a small but significant reduction in BMdDC survival was observed upon SCF silencing. Incubation of BMdDCs with SCF did not modulate antigen presentation ability of these cells, nor it did regulate their membrane expression of the chemokine receptor CXCR4. We conclude that the SCF/c-kit mediated pro-survival circuit may have been overlooked because of the prominent use of GM-CSF in DC cultures in vitro, including those human DC cultures destined for the clinics. We speculate that DCs more prominently rely on SCF in vivo in some microenvironments, with potential implications for Graft Versus Host Disease (GVHD) and anti-tumor immunity

Effect of polyphenols dietary grape by-products on chicken patties

An experiment was conducted to study the dietary effect that the inclusion (40 g kg) of grape seed (GS), grape skin (SS), grape pomace (GP), and (0.2 g kg) of vitamin E (E) had on the composition and microbiological quality of chicken breast meat and on the physico-chemical parameters (TBARS, pH, color, Kramer shear force), sensorial characteristics, and microbiological quality of chicken breast meat patties during chilled storage (0, 3, 6, and 9 days) at 2 °C. In general, proximate composition and microbial counts of the raw chicken breast meat and the patties were not affected. Lower TBARS values were detected in patties formulated with breast meat obtained from birds fed E, SS, and GP diets. No clear effect was observed on the color or textural characteristics of the different patties. The addition of SS and GP in chicken diets reduced TBARS values showing some improvement in the oxidative stability of breast patties without affecting its technological properties, sensorial attributes, or microbial quality.The authors thank the MINECO and CSIC for financial support of Projects AGL2012-31355/GAN, AGL2014-53207-C2-1-R, and the Intramural 2014470E073. In addition, we are grateful to CAM and ESI Funds for financially supporting project MEDGAN-CM S2013/ABI2913). We would also like to thank MIUR and UNIMOL for the Ph.D. fellowship of Maria Nardoia.Peer Reviewe