35 research outputs found
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
Supplementary Material for: Findings of Vascular Brain Injury and Structural Loss from Cranial Magnetic Resonance Imaging in Elderly American Indians: The Strong Heart Study
<p><b><i>Background:</i></b> The Cerebrovascular Disease and its
Consequences in American Indians study conducted cranial MRI examination
of surviving participants of the Strong Heart Study, a longitudinal
cohort of elderly American Indians. <b><i>Methods:</i></b> Of the 1,033 recruited participants, some were unable to complete the MRI (<i>n</i> = 22), some scans were unusable due to participant motion or technical errors (<i>n</i> = 13), and one community withdrew consent after data collection (<i>n</i>
= 209), leaving 789 interpretable MRI scan images. Six image sequences
were obtained in contiguous slices on 1.5T scanners. Neuroradiologists
graded white matter hyperintensities (WMH), sulci, and ventricles on a
0- to 9-point scale, and recorded the presence of infarcts and
hemorrhages. Intracranial, brain, hippocampal, and WMH volumes were
estimated by automated image processing. <b><i>Results:</i></b> The
median scores for graded measures were 2 (WMH) and 3 (sulci,
ventricles). About one-third of participants had lacunar (20%) or other
infarcts (13%); few had hemorrhages (5.7%). Findings of cortical atrophy
were also prevalent. Statistical analyses indicated significant
associations between older age and findings of vascular injury and
atrophy; male gender was associated with findings of cortical atrophy. <b><i>Conclusions:</i></b>
Vascular brain injury is the likely explanation in this elderly
American Indian population for brain infarcts, hemorrhages, WMH grade,
and WMH volume. Although vascular brain injury may play a role in other
findings, independent degenerative other disease processes may underlie
abnormal sulcal widening, ventricular enlargement, hippocampal volume,
and total brain volume. Further examination of risk factors and outcomes
with these findings may expand the understanding of neurological
conditions in this understudied population.</p
Recommended from our members
Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid-derived suppressor cells
Preclinical modeling of surgery and steroid therapy for glioblastoma reveals changes in immunophenotype that are associated with tumor growth and outcome
PURPOSE: Glioblastoma (GBM) immunotherapy clinical trials are generally initiated after standard-of-care treatment, including surgical resection, perioperative high-dose steroid therapy, chemotherapy, and radiation treatment, has either begun or failed. However, the impact of these interventions on the anti-tumoral immune response is not well studied. While discoveries regarding the impact of chemotherapy and radiation on immune response have been made and translated into clinical trial design, the impact of surgical resection and steroids on the anti-tumor immune response has yet to be determined. EXPERIMENTAL DESIGN: We developed a murine model integrating tumor resection and steroid treatment and used flow cytometry to analyze systemic and local immune changes. These mouse model findings were validated in a cohort of 95 primary GBM patients. RESULTS: Using our murine resection model, we observed a systemic reduction in lymphocytes corresponding to increased tumor volume and decreased circulating lymphocytes that was masked by dexamethasone treatment. The reduction in circulating T cells was due to reduced CCR7 expression, resulting in T-cell sequestration in lymphoid organs and the bone marrow. We confirmed these findings in a cohort of primary GBM patients and found that prior to steroid treatment, circulating lymphocytes inversely correlated with tumor volume. Lastly, we demonstrated that peripheral lymphocyte content varies with progression-free and overall survival, independent of tumor volume, steroid use, or molecular profiles. CONCLUSIONS: These data reveal that prior to intervention, increased tumor volume corresponds with reduced systemic immune function and that peripheral lymphocyte counts are prognostic when steroid treatment is taken into account
Data presented in the paper “Plants face the flow in V-formation: a study of plant patch alignment in streams”
This dataset contains the field observations and experimental data presented in the paper “Plants face the flow in V-formation: a study of plant patch alignment in streams”, with the above contributors as authors, submitted to Limnology and Oceanography. The dataset contains the underlying data (drag and hydrodynamic measurements, and temporal in-stream vegetation surveys) presented in the manuscript
Recommended from our members
Global immune fingerprinting in glioblastoma patient peripheral blood reveals immune-suppression signatures associated with prognosis
Recommended from our members