title: DNA methylation in repetitive elements and Alzheimer disease.
abstract: Epigenetics is believed to play a role in Alzheimer's disease (AD). DNA methylation, the most investigated epigenetic hallmark, is a reversible mechanism that modifies genome function and chromosomal stability through the addition of methyl groups to cytosine located in CpG dinucleotides to form 5 methylcytosine (5mC). Methylation status of repetitive elements (i.e. Alu, LINE-1 and SAT-α) is a major contributor of global DNA methylation patterns and has been investigated in relation to a variety of human diseases. However, the role of methylation of repetitive elements in blood of AD patients has never been investigated so far. In the present study, a quantitative bisulfite-PCR pyrosequencing method was used to evaluate methylation of Alu, LINE-1 and SAT-α sequences in 43 AD patients and 38 healthy donors. In multivariate analysis adjusting for age and gender, LINE-1 was increased in AD patients compared with healthy volunteers (ADs: 83.6%5mC, volunteers: 83.1%5mC, p-value: 0.05). The group with best performances in mini mental state examination (MMSE) showed higher levels of LINE-1 methylation compared to the group with worst performances (MMSE>22: 83.9%5mC; MMSE≤22: 83.2%5mC; p=0.05). Our data suggest that LINE-1 methylation may lead to a better understanding of AD pathogenesis and course, and may contribute to identify novel markers useful to assess risk stratification. Further prospective investigations are warranted to evaluate the dynamics of DNA methylation from early-stage AD to advanced phases of the disease.
authors.affiliation: Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy. valentina.bollati@unimi.it
authors.forename: V
authors.initials: V
authors.lastname: Bollati
authors.forename: D
authors.initials: D
authors.lastname: Galimberti
authors.forename: L
authors.initials: L
authors.lastname: Pergoli
authors.forename: E
authors.initials: E
authors.lastname: Dalla Valle
authors.forename: F
authors.initials: F
authors.lastname: Barretta
authors.forename: F
authors.initials: F
authors.lastname: Cortini
authors.forename: E
authors.initials: E
authors.lastname: Scarpini
authors.forename: P A
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: A
authors.initials: A
authors.lastname: Baccarelli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020087:Alu Elements / Q000235:genetics*; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D019175:DNA Methylation; D004276:DNA, Satellite / Q000235:genetics*; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011581:Psychological Tests; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D004276:DNA, Satellite; C054369:MAPT protein, human; D016875:tau Proteins