Dataset Information
Progranulin levels in blood in Alzheimer's disease and mild cognitive impairment.
Ontology highlight
ABSTRACT:
Methods: Peripheral blood progranulin gene expression was measured, using microarrays from Alzheimer's (n = 186), MCI (n = 118), and control (n = 204) subjects from the University of California San Francisco Memory and Aging Center (UCSF-MAC) and two independent published series (AddNeuroMed and ADNI). GRN gene expression was correlated with clinical, demographic, and genetic data, including APOE haplotype and the GRN 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 GRN promoter methylation in males (P = 0.007). Progranulin expression was 13% higher in AD and MCI patients compared with controls in the UCSF-MAC cohort (F2,505 = 10.41, P = 3.72*10-5). This finding was replicated in the AddNeuroMed (F2,271 = 17.9, P = 4.83*10-8) but not the ADNI series. The rs5848 SNP (T-allele) predicted decreased blood progranulin gene expression (P = 0.03). The APOE4 haplotype was positively associated with progranulin expression independent of diagnosis (P = 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.
SUBMITTER: Cooper YA
PROVIDER: S-EPMC5945969 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
Publications
Progranulin levels in blood in Alzheimer's disease and mild cognitive impairment.
Annals of clinical and translational neurology 20180402 5
<h4>Objective</h4>Changes in progranulin (<i>GRN</i>) expression have been hypothesized to alter risk for Alzheimer's disease (AD). We investigated the relationship between <i>GRN</i> expression in peripheral blood and clinical diagnosis of AD and mild cognitive impairment (MCI).<h4>Methods</h4>Peripheral blood progranulin gene expression was measured, using microarrays from Alzheimer's (<i>n</i> = 186), MCI (<i>n</i> = 118), and control (<i>n</i> = 204) subjects from the University of Californi ...[more]
