Progranulin levels in blood in Alzheimer's disease and mild cognitive impairment
| Autor: | Giovanni Coppola, Anna Karydas, Bruce L. Miller, Ginette Serrero, Deepika Dokuru, Zhongan Yang, Adam L. Boxer, Daniel Nachun, Binbin Yue, Yonatan A. Cooper |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Oncology medicine.medical_specialty Aging Clinical Sciences Neurodegenerative Alzheimer's Disease 03 medical and health sciences 0302 clinical medicine Polymorphism (computer science) Internal medicine Gene expression mental disorders medicine Genetics Acquired Cognitive Impairment SNP 2.1 Biological and endogenous factors Aetiology Alzheimer's Disease Related Dementias (ADRD) Research Articles business.industry General Neuroscience Haplotype Alzheimer's Disease Neuroimaging Initiative Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Methylation medicine.disease 3. Good health Brain Disorders 030104 developmental biology DNA methylation Neurological Dementia Neurology (clinical) business 030217 neurology & neurosurgery Frontotemporal dementia Research Article |
| Zdroj: | Cooper, YA; Nachun, D; Dokuru, D; Yang, Z; Karydas, AM; Serrero, G; et al.(2018). Progranulin levels in blood in Alzheimer's disease and mild cognitive impairment. ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 5(5), 616-629. doi: 10.1002/acn3.560. UCLA: Retrieved from: http://www.escholarship.org/uc/item/7rx4w3n8 Annals of clinical and translational neurology, vol 5, iss 5 Annals of Clinical and Translational Neurology |
| Popis: | Author(s): Cooper, Yonatan A; Nachun, Daniel; Dokuru, Deepika; Yang, Zhongan; Karydas, Anna M; Serrero, Ginette; Yue, Binbin; Alzheimer's Disease Neuroimaging Initiative; Boxer, Adam L; Miller, Bruce L; Coppola, Giovanni | Abstract: ObjectiveChanges in progranulin (GRN) expression have been hypothesized to alter risk for Alzheimer's disease (AD). We investigated the relationship between GRN expression in peripheral blood and clinical diagnosis of AD and mild cognitive impairment (MCI).MethodsPeripheral 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.ResultsWe 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.InterpretationProgranulin 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. |
| Databáze: | OpenAIRE |
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