衰老的表观基因组:整合性分析揭示了与阿尔茨海默病的功能重叠
Wei Zhang1, David Lukacsovich1, Juan I Young2,3
1Division of Biostatistics, Department of Public Health Sciences, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
medRxiv : the preprint server for health sciences
|June 30, 2025
概括
血液中的老化DNA甲基化变化与阿尔茨海默病 (AD) 风险有关. 这项研究确定了与衰老和AD相关的特定甲基化位点,表明了早期检测潜在的基于血液的生物标志物.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 神经科学是一个神经科学.
- 老年学是一门学科.
背景情况:
- 老龄化是阿尔茨海默病 (AD) 的主要危险因素.
- 血液中与年龄相关的DNA甲基化 (DNAm) 和AD病原体之间的联系尚不清楚.
- 研究血液DNAm可以提供关于AD机制和潜在生物标志物的见解.
研究的目的:
- 为了识别血液中与年龄相关的DNA甲基化模式.
- 确定这些模式与阿尔茨海默病风险的相关性.
- 提名潜在的血基生物标志物用于AD.
主要方法:
- 血液DNAm数据的元分析来自两个独立的队列 (弗雷明汉姆心脏研究和阿尔茨海默病神经成像倡议).
- 根据年龄,性别,免疫细胞比例和批量效应进行统计调整.
- 路径丰富,局部化和外部验证分析.
主要成果:
- 确定了3758个CpG和556个不同甲基化区域 (DMR),与衰老有着一致的关联.
- 途径分析揭示了免疫反应,代谢调节和突触可塑性的丰富.
- 发现与衰老相关的DNAm和AD/神经病理学之间存在显著的重叠,32个区域显示出共同的遗传影响.
- 优先考虑9个与衰老相关的CpG,具有血液到大脑甲基化一致性和AD相关性.
结论:
- 血液中与年龄相关的DNA甲基化与阿尔茨海默病有功能性联系.
- 与衰老相关的特定DNAm位点可以作为AD的有价值的生物标志物.
- 这些发现增强了对衰老和AD病变发生之间的相互作用的理解.
更多相关视频
04:41Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
Published on: January 9, 2020
19.1K
09:38Generalized Psychophysiological Interaction PPI Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
15.1K
相关概念视频
Alzheimer's Disease: Overview
678
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
678
Aging
193
Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
193
The Effect of Aging on Tissues
2.6K
Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
2.6K
Alzheimer's Disease: Treatment
265
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
265
Epigenetic Regulation
3.1K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.1K
Epistasis Analysis
5.2K
Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...
5.2K
