Peripheral leukocyte expression of the potential biomarker proteins Bdnf, Sirt1, and Psen1 is not regulated by promoter methylation in Alzheimer's disease patients

Carboni, Lucia; Lattanzio, Francesca; Candeletti, Sanzio; Porcellini, Elisa; Raschi, Elena; Licastro, Federico; Romualdi, Patrizia

doi:10.1016/j.neulet.2015.08.012

Cited by 34 publications

(19 citation statements)

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“…Alternatively, two studies [50, 51] showed no difference in DNA methylation of APP in brain tissue between AD and healthy controls. Fourteen studies found no difference or clear pattern in methylation of the following genes: 12-LOX [34], debrin-like protein gene [34], p450 epoxygenase gene [34], MAPT , PSEN1 , UCHL1 , SST [52], SSTR4 [52], F2RL2 [45], SOD-1 [48] and GRN [53] in brain tissue; PS1 [49], PS2 [49] and tau1 [49], SMARCA 5 [54], CHD1 [54], BDNF [55], SIRT1 [55], PSEN1 [55{Tannorella, 2015 #2823], genes involved in DNA repair [56], genes involved in homocysteine pathway [57], CTSB [58], CTSD [58], DDT [58], TSC1 [58], NRD1 [58] and NDUFA6 [58] in blood cells; HSPA8 [59], HSPA9 [59], ApoE4 [47, 49], SNAP25 [60], SORL 1 , SIRT1 and SIRT3 [49, 54, 60] in both blood cells and brain tissue (Table 2). However, 7 studies showed differences in methylation patterns of CpG sites (within same gene some CpG sites were hypomethylated and some others were hypermethylated, in AD cases) examined at the following genes: SORL1 [61], ABCA7 [61], SLC2A4 [61], BIN1 [61], HSPA8 [59], HSPA9 [59], DR4 gene [62], BDNF4 [43, 44], SIRT1 [49], APP [47], MAPT [47] and GSK3B [47].…”

Section: Resultsmentioning

confidence: 99%

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review

et al. 2016

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ImportanceEpigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD).ObjectiveTo systematically review studies investigating epigenetic marks in AD or PD.MethodsEleven bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form.ResultsOf 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes). There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue) in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of α-synuclein gene (SNCA) was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD.ConclusionMany studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.

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Section: Resultsmentioning

confidence: 99%

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review

et al. 2016

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“…Similarly, Nagata et al (2015) reported higher DNA methylation affecting a single CpG site in the BDNF promoter of patients with AD. Nevertheless, it is important to note that Carboni et al (2015) could not confirm methylation alterations in the BDNF promoter in peripheral blood of Alzheimer's disease patients. Therefore, doubts remain as to whether BDNF promoter methylation changes occur in AD patients.…”

Section: Alzheimer's Diseasementioning

confidence: 90%

DNA Methylation Biomarkers in Aging and Age-Related Diseases

2020

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Recent research efforts provided compelling evidence of genome-wide DNA methylation alterations in aging and age-related disease. It is currently well established that DNA methylation biomarkers can determine biological age of any tissue across the entire human lifespan, even during development. There is growing evidence suggesting epigenetic age acceleration to be strongly linked to common diseases or occurring in response to various environmental factors. DNA methylation based clocks are proposed as biomarkers of early disease risk as well as predictors of life expectancy and mortality. In this review, we will summarize key advances in epigenetic clocks and their potential application in precision health. We will also provide an overview of progresses in epigenetic biomarker discovery in Alzheimer's, type 2 diabetes, and cardiovascular disease. Furthermore, we will highlight the importance of prospective study designs to identify and confirm epigenetic biomarkers of disease.

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“…While these two studies conflict with the findings from our analysis, involving a larger cohort of population-based individuals, a third case-control reported findings that support those of our work. This study involving Caucasian Italian men (20 AD, 19 controls; mean age 75 (SD 7), found no association between blood BDNF methylation and AD status [22]. AD was diagnosed using the DSM-III-R and NINCDS/ADRDA criteria, including cognitive assessments using MMSE.…”

Section: Discussionmentioning

confidence: 83%

“…Two small case-control studies (n=106 and 18) reported higher BDNF DNA methylation in dementia cases compared to controls [20,21]. A third study (n=39) however, found no association [22]. Importantly, all three studies investigated DNA methylation in individuals with dementia, so they could not conclude whether these marks were present prior to diagnosis, and thus their potential as pre-symptomatic biomarkers is unknown.…”

Section: Introductionmentioning

confidence: 99%

Is Peripheral BDNF Promoter Methylation a Preclinical Biomarker of Dementia?

Fransquet

Ritchie

Januar

et al. 2020

JAD

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Brain derived neurotrophic factor (BDNF) has been implicated in dementia. Preliminary evidence suggests that BDNF DNA methylation may be a diagnostic biomarker of dementia, but the potential pre-clinical utility remains unclear. Participants in the ESPRIT study were assessed for cognitive function and dementia (DSM-IV criteria) over 14-years. BDNF exon 1 promoter methylation was measured in blood at baseline (n=769), and buccal samples during follow-up (n=1062). Genotyping was carried out for several common BDNF SNPs, including Val66Met (rs6265) and APOE-ɛ4. Multivariable logistic regression analyses determined the association between BDNF methylation and both prevalent and incident dementia. Adjustment for gender, age, education, APOE-ε4 genotype, body mass index, depression, and type 2 diabetes, as well as possible effect modification by gender and genetic variation were also investigated. Weak evidence of an association between lower blood methylation and dementia was observed at one of 11 sites investigated (Δ-0.5%, 95%CI:-0.9,-0.04, p=0.03, p=0.22 adjusted for multiple comparisons). Buccal methylation at two other sites was associated with 14-year incident dementia cases prior to adjustment for multiple comparisons only, and the effect sizes were small (Δ+0.3%, OR:1.57, SE:0.30, p=0.02, p=0.14 adjusted and Δ-1.5%, OR:0.85, SE:0.06, p=0.03, p=0.14 adjusted). Genetic variation in the BDNF gene did not modify these associations, and no gender-specific effects were observed. There was only a weak correlation between blood and buccal BDNF log-methylation at two sites (both r=-0.11). There was no strong evidence that blood or buccal BDNF exon 1 promoter DNA methylation is associated with prevalent or incident dementia, and reported associations would not remain after adjustment for multiple testing.

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Peripheral leukocyte expression of the potential biomarker proteins Bdnf, Sirt1, and Psen1 is not regulated by promoter methylation in Alzheimer's disease patients

Cited by 34 publications

References 40 publications

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review

DNA Methylation Biomarkers in Aging and Age-Related Diseases

Is Peripheral BDNF Promoter Methylation a Preclinical Biomarker of Dementia?

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