Objective: Changes in progranulin () expression have been hypothesized to alter risk for Alzheimer's disease (AD). We investigated the relationship between expression in peripheral blood and clinical diagnosis of AD and mild cognitive impairment (MCI).
Methods: Peripheral blood progranulin gene expression was measured, using microarrays from Alzheimer's ( = 186), MCI ( = 118), and control ( = 204) subjects from the University of California San Francisco Memory and Aging Center (UCSF-MAC) and two independent published series (AddNeuroMed and ADNI). gene expression was correlated with clinical, demographic, and genetic data, including APOE haplotype and the rs5848 single-nucleotide polymorphism. Finally, we assessed progranulin protein levels, using enzyme-linked immunosorbent assay, and methylation status using methylation microarrays.
Results: We observed an increase in blood progranulin gene expression and a decrease in promoter methylation in males ( = 0.007). Progranulin expression was 13% higher in AD and MCI patients compared with controls in the UCSF-MAC cohort ( = 10.41, = 3.72*10). This finding was replicated in the AddNeuroMed ( = 17.9, = 4.83*10) but not the ADNI series. The rs5848 SNP (T-allele) predicted decreased blood progranulin gene expression ( = 0.03). The APOE4 haplotype was positively associated with progranulin expression independent of diagnosis ( = 0.04). Finally, we did not identify differences in plasma progranulin protein levels or gene methylation between diagnostic categories.
Interpretation: Progranulin mRNA is elevated in peripheral blood of patients with AD and MCI and its expression is associated with numerous genetic and demographic factors. These data suggest a role in the pathogenesis of neurodegenerative dementias besides frontotemporal dementia.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945969 | PMC |
http://dx.doi.org/10.1002/acn3.560 | DOI Listing |
Curr Protein Pept Sci
January 2025
Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, Karachi-75270, Pakistan.
Background: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a high recurrence rate. A new therapeutic intervention is urgently needed to combat this lethal subtype. The identification of biomarkers is also crucial for improving outcomes in TNBC.
View Article and Find Full Text PDFCurr Pharm Des
January 2025
Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
Introduction: Sepsis, like neutropenic sepsis, is a medical condition in which our body overreacts to infectious agents. It is associated with damage to normal tissues and organs by the immune system, which leads to the spread of inflammation throughout our body. Of note, microRNAs (miRNAs) have been found to have a critical role in the sepsis progression.
View Article and Find Full Text PDFCurr Cancer Drug Targets
January 2025
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India.
Cancer manifests as uncontrolled cell proliferation. Tankyrase, a poly(ADP-ribose) polymerase member, is vital in Wnt signal transmission, making it a promising cancer therapy target. The Wnt/β-catenin pathway regulates critical biological processes like genomic stability, gene expression, energy utilization, and apoptosis.
View Article and Find Full Text PDFBackground: Axial Spondyloarthritis (axSpA) is a chronic inflammatory rheumatic condition affecting the axial skeleton, leading to pain, stiffness, and fatigue. While biologic therapies have improved clinical management, many patients experience partial or no responses, resulting in delays in disease control. Additionally, the risk of adverse events and increased costs remains a concern.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:
CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!