title: Methylation analysis of SST and SSTR4 promoters in the neocortex of Alzheimer's disease patients.
abstract: Several observations have pointed to a major pathogenic role of somatostatin depletion with respect to amyloid accumulation, which is often thought to be the crucial event in a cascade leading to Alzheimer's disease (AD). As methylation of CpG islands plays an important role in gene silencing, we studied the methylation status of the CpG islands in the promoters of somatostatin (SST) and in that of its receptor subtype in the cerebral cortex, SSTR4, in tissue samples from the middle temporal (Brodmann area 22) and superior frontal gyrus (Brodmann area 9) of 5 severely affected AD patients aged 72-94 years (Braak stages V-C or VI-C) and 5 non-demented controls aged 50-92 years. Bisulfite sequencing of DNA from cortical gray and infracortical white matter showed that the DNA methylation status at the promoters of SST and SSTR4 did not significantly differ between AD and control samples in any of the regions analyzed. We confirmed these results using deep bisulfite sequencing of PCR products from the SST promoter amplified from DNA from the cortical gray of the superior frontal gyrus of all AD patients and non-demented controls. We observed a trend toward increased DNA methylation with increasing age. In conclusion, deregulated somatostatin signaling in the AD cortices studied cannot be explained by hypermethylation of the SST or SSTR4 promoter CpG islands.
authors.affiliation: Institute of Human Genetics, Faculty of Medicine, University Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Grosser
authors.affiliation: Institute of Human Genetics, Faculty of Medicine, University Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Neumann
authors.affiliation: Institute of Human Genetics, Faculty of Medicine, University Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
authors.affiliation: Institute of Human Genetics, Faculty of Medicine, University Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Zeschnigk
authors.affiliation: Institute of Neuropathology, Faculty of Medicine, University Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany. Electronic address: johannes.nes@uk-essen.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: van de Nes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*
chemical_list: D017481:Receptors, Somatostatin; C098681:somatostatin receptor subtype-4; D013004:Somatostatin
keywords: Alzheimer's disease; DNA methylation; Epigenetics; Human brain; Next-generation sequencing; Somatostatin