The effect of epigenetic aging on neurodegenerative diseases: a Mendelian randomization study DOI Creative Commons

Jingqi Fan,

Qing Liu, Xin Liu

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: May 10, 2024

Aging has always been considered as a risk factor for neurodegenerative diseases, but there are individual differences and its mechanism is not yet clear. Epigenetics may unveil the relationship between aging diseases. Our study employed bidirectional two-sample Mendelian randomization (MR) design to assess potential causal association epigenetic We utilized publicly available summary datasets from several genome-wide studies (GWAS). investigation focused on multiple measures of age exposures outcomes, while occurrence diseases served outcomes. Sensitivity analyses confirmed accuracy results. The results show significant decrease in Parkinson's disease with GrimAge (OR = 0.8862, 95% CI 0.7914-0.9924, p 0.03638). Additionally, we identified that HannumAge was linked an increased Multiple Sclerosis 1.0707, 1.0056-1.1401, 0.03295). Furthermore, also found estimated plasminogen activator inhibitor-1(PAI-1) levels demonstrated Alzheimer's 1.0001, 1.0000-1.0002, 0.04425). Beyond that, did observe any associations risk. findings firstly provide evidence Exploring perspective contribute diagnosis, prognosis, treatment

Language: Английский

Epigenome-wide association study of incident type 2 diabetes in Black and White participants from the Atherosclerosis Risk in Communities Study DOI

Sowmya Venkataraghavan,

James S. Pankow,

Eric Boerwinkle

et al.

Diabetologia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Language: Английский

Citations

2
Cell-type heterogeneity: Why we should adjust for it in epigenome and biomarker studies DOI Creative Commons
Q. Luo, Andrew E. Teschendorff

Clinical Epigenetics, Journal Year: 2022, Volume and Issue: 14(1)

Published: Feb. 28, 2022

Abstract Most studies aiming to identify epigenetic biomarkers do so from complex tissues that are composed of many different cell-types. By definition, these cell-types vary substantially in terms their profiles. This cell-type specific variation among healthy cells is completely independent the associated with disease, yet it dominates variability landscape. While composition can change disease and this may provide accurate reproducible biomarkers, not adjusting for underlying heterogeneity seriously limit sensitivity precision detect disease-relevant or hamper our understanding such biomarkers. Given computational experimental tools tackling available, we here stress future biomarker should aim estimates fractions all samples study, before after adjustment heterogeneity, order obtain a more complete unbiased picture biomarker-landscape. critical, only improve reproducibility eventual clinical application but importantly, also molecular itself.

Language: Английский

Citations

46
Blood DNA methylation signature for incident dementia: Evidence from longitudinal cohorts DOI Creative Commons
Wei Zhang,

Juan I. Young,

Lissette Gomez

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Distinguishing between molecular changes that precede dementia onset and those resulting from the disease is challenging with cross-sectional studies. We studied blood DNA methylation (DNAm) differences incident in two large longitudinal cohorts: Offspring cohort of Framingham Heart Study (FHS) Alzheimer's Disease Neuroimaging Initiative (ADNI) study. analyzed DNAm samples > 1000 cognitively unimpaired subjects. Meta-analysis identified 44 CpGs differentially methylated regions consistently associated time to both cohorts. Our integrative analysis early processes dementia, such as immune responses metabolic dysfunction. Furthermore, we developed a methylation-based risk score, which successfully predicted future cognitive decline an independent validation set, even after accounting for age, sex, apolipoprotein E ε4, years education, baseline diagnosis, Mini-Mental State Examination score. offers promising source biomarker assessment. Blood at individual are significantly dementia. Pathway revealed enriched biological pathways involved processes. Out-of-sample demonstrated score dataset,

Language: Английский

Citations

1
Utility of DNA Methylation as a Biomarker in Aging and Alzheimer’s Disease DOI Creative Commons
Lidija Milicic, Tenielle Porter, Michaël Vacher

et al.

Journal of Alzheimer s Disease Reports, Journal Year: 2023, Volume and Issue: 7(1), P. 475 - 503

Published: May 15, 2023

Epigenetic mechanisms such as DNA methylation have been implicated in a number of diseases including cancer, heart disease, autoimmune disorders, and neurodegenerative diseases. While it is recognized that tissue-specific, limitation for many studies the ability to sample tissue interest, which why there need proxy blood, reflective state target tissue. In last decade, has utilized design epigenetic clocks, aim predict an individual’s biological age based on algorithmically defined set CpGs. A found associations between disease and/or risk with increased age, adding weight theory being linked processes. Hence, this review takes closer look at utility biomarker aging particular focus Alzheimer’s disease.

Language: Английский

Citations

17
An Epigenetic Manifestation of Alzheimer's Disease: DNA Methylation DOI Open Access

Boyi Feng,

Junli Zheng,

Ying Cai

et al.

Actas Españolas de Psiquiatría, Journal Year: 2024, Volume and Issue: 52(3), P. 365 - 374

Published: June 5, 2024

Alzheimer's disease (AD), the most common form of dementia, has a complex pathogenesis. The number AD patients increased in recent years due to population aging, while trend toward younger age onset arisen, imposing substantial burden on society and families, garnering extensive attention. DNA methylation recently been revealed play an important role progression. is critical mechanism regulating gene expression, alterations this dysregulate expression disrupt pathways, including oxidative stress responses, inflammatory reactions, protein degradation processes, eventually resulting disease. Studies have widespread changes patients' peripheral blood brain tissues, affecting multiple signaling pathways severely impacting neuronal cell synaptic functions. This review summarizes pathogenesis AD, aiming provide theoretical basis for its early prevention treatment.

Language: Английский

Citations

7
Epigenetic Peripheral Biomarkers for Early Diagnosis of Alzheimer’s Disease DOI Open Access
Chiara Villa, Andrea Stoccoro

Genes, Journal Year: 2022, Volume and Issue: 13(8), P. 1308 - 1308

Published: July 22, 2022

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and represents the leading cause of cognitive impairment dementia in older individuals throughout world. The main hallmarks AD include brain atrophy, extracellular deposition insoluble amyloid-β (Aβ) plaques, intracellular aggregation protein tau neurofibrillary tangles. These pathological modifications start many years prior to clinical manifestations

Language: Английский

Citations

25
Identification of candidate DNA methylation biomarkers related to Alzheimer’s disease risk by integrating genome and blood methylome data DOI Creative Commons
Yanfa Sun, Jingjing Zhu, Yaohua Yang

et al.

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 13, 2023

Abstract Alzheimer disease (AD) is a common neurodegenerative with late onset. It critical to identify novel blood-based DNA methylation biomarkers better understand the extent of molecular pathways affected in AD. Two sets blood genetic prediction models developed using different reference panels and modelling strategies were leveraged evaluate associations genetically predicted levels AD risk 111,326 (46,828 proxy) cases 677,663 controls. A total 1,168 cytosine-phosphate-guanine (CpG) sites showed significant association at false discovery rate (FDR) < 0.05. Methylation 196 CpG correlated expression 130 adjacent genes blood. Overall, 52 32 consistent directions for methylation-gene expression-AD risk, including nine ( CNIH4 , THUMPD3 SERPINB9 MTUS1 CISD1 FRAT2 CCDC88B FES SSH 2) firstly reported as genes. Nine enriched dementia categories P values ranged from 1.85 × 10 -4 7.46 -6 ), 19 neurological network (score = 54) also observed. Our findings improve understanding genetics etiology

Language: Английский

Citations

16
Advances in the role of the GADD45 family in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders DOI Creative Commons

Mengbing Huang,

Ji Wang, Wei Liu

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Jan. 25, 2024

The growth arrest and DNA damage inducible protein 45 (GADD45) family comprises stress-induced nuclear proteins that interact with demethylases to facilitate demethylation, thereby regulating diverse cellular processes including oxidative stress, repair, apoptosis, proliferation, differentiation, inflammation, neuroplasticity by modulating the expression patterns of specific genes. Widely expressed in central nervous system, GADD45 plays a pivotal role various neurological disorders, rendering it potential therapeutic target for system diseases. This review presented comprehensive overview mechanisms action associated each member (GADD45α, GADD45β, GADD45γ) neurodevelopmental, neurodegenerative, neuropsychiatric while also explored strategies harness these intervention treatment. Future research should prioritize development effective modulators targeting clinical trials aimed at treating

Language: Английский

Citations

6
Downregulation of Ambra1 by altered DNA methylation exacerbates dopaminergic neuron damage in a fenpropathrin-induced Parkinson-like mouse model DOI Creative Commons
Songzhe He, Qi Qu, Xi Chen

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 271, P. 115995 - 115995

Published: Jan. 20, 2024

Language: Английский

Citations

5
DNA methylation and stroke prognosis: an epigenome-wide association study DOI Creative Commons
Joan Jiménez-Baladó, Isabel Fernández, Cristina Gallego-Fábrega

et al.

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: June 6, 2024

Abstract Background and aims Stroke is the leading cause of adult-onset disability. Although clinical factors influence stroke outcome, there a significant variability among individuals that may be attributed to genetics epigenetics, including DNA methylation (DNAm). We aimed study association between DNAm prognosis. Methods results To aim, we conducted two-phase (discovery-replication meta-analysis) in Caucasian patients with ischemic from two independent centers (BasicMar [discovery, N = 316] St. Pau [replication, 92]). Functional outcome was assessed using modified Rankin Scale (mRS) at three months after stroke, being poor defined as mRS > 2. determined 450K EPIC BeadChips whole-blood samples collected within first 24 h. searched for differentially methylated positions (DMPs) 370,344 CpGs, candidates below p -value < 10 –5 were subsequently tested replication cohort. then meta-analyzed DMP both cohorts used them identify regions (DMRs). After doing epigenome-wide study, found 29 DMPs one replicated: cg24391982, annotated thrombospondin-2 ( THBS2 ) gene discovery 1.54·10 –6 ; 9.17·10 –4 meta-analysis 6.39·10 –9 ). Besides, four DMRs identified zinc finger protein 57 homolog ZFP57 ), Arachidonate 12-Lipoxygenase 12S Type ALOX12 ABI Family Member 3 ABI3 Allantoicase ALLC genes 1·10 all cases). Discussion Patients showed ZFP57, ALOX12, genes. This suggests an DNAm, which help new recovery mechanisms.

Language: Английский

Citations

5