Peripheral leukocyte expression of the potential biomarker proteins Bdnf, Sirt1, and Psen1 is not regulated by promoter methylation in Alzheimer's disease patients.
The identification of Alzheimer's disease (AD) biomarkers is crucial to support drug discovery. Within putative biomarkers, peripheral Bdnf levels correlate with cognitive decline and AD, although conflicting findings are reported. Sirtuin 1 (Sirt1) serum levels are lower in AD patients and Presenilin 1 (Psen1) is expressed by blood cells. DNA methylation is altered in AD patients, suggesting that epigenetic mechanisms play a role in AD pathophysiology. The objective of this study was to investigate promoter methylation levels of potential biomarkers in AD cases and controls. Peripheral blood DNA methylation levels were analysed by methylation-specific primer real-time PCR. Bdnf promoter methylation levels did not differ between AD patients and controls. Similarly, Sirt1 promoter revealed minimal levels of methylation which did not display significant differences between groups. No significant difference was revealed between AD patients and controls also in Psen1 methylation, showing a large variability of values among subjects. Although peripheral Bdnf expression is associated with differential promoter methylation in psychiatric and neurological disorders, our results suggest that different mechanisms take place in AD. The finding that the control of Sirt1 protein levels in blood is not exerted through the repression of mRNA expression by promoter hypermethylation is in agreement with previous data. In contrast, other studies reported that Psen1 methylation may be increased or decreased in AD patients, suggesting that additional studies are required. In conclusion, this study shows that peripheral levels of the potential AD biomarker proteins Bdnf, Sirt1, and Psen1 are not regulated by different promoter methylation.
Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum University of Bologna, Bologna, Italy. Electronic address: lucia.carboni4@unibo.it.
Lucia
L
Carboni
Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum University of Bologna, Bologna, Italy.
Francesca
F
Lattanzio
Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum University of Bologna, Bologna, Italy.
Sanzio
S
Candeletti
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, Bologna, Italy.
Elisa
E
Porcellini
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, Bologna, Italy.
Elena
E
Raschi
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, Bologna, Italy.
Federico
F
Licastro
Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum University of Bologna, Bologna, Italy.
Patrizia
P
Romualdi
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008745:Methylation; D053764:Presenilin-1 / Q000097:blood / Q000235:genetics*; D011401:Promoter Regions, Genetic; D056564:Sirtuin 1 / Q000097:blood / Q000235:genetics*
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; C508853:PSEN1 protein, human; D053764:Presenilin-1; C579455:BDNF protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1
Alzheimer disease; Biomarkers; Brain derived neurotrophic factor; DNA methylation; Presenilin 1; Sirtuin 1