罕见遗传变异对阿尔茨海默病的影响
Lara De Deyn1,2, Kristel Sleegers3,4
1Complex Genetics of Alzheimer's Disease group, VIB-UAntwerp Center for Molecular Neurology, Antwerp, Belgium.
Nature reviews. Neurology
|February 5, 2025
概括
罕见的遗传变异对阿尔茨海默病 (AD) 风险有显著的贡献,为疾病机制和潜在的药物标提供了新的见解. 了解这些罕见变异对于预测AD发展和推进治疗策略至关重要.
科学领域:
- 遗传学 遗传学 是一个
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 阿尔茨海默病 (AD) 是一种进展性神经退行性疾病,具有重要的遗传基础.
- 虽然主导突变和常见变异已得到充分研究,但导致多基因AD的遗传因素,特别是罕见变异,仍然在很大程度上是未知的.
- 罕见的变体越来越多地被认可,因为它们有可能解释AD缺失的遗传性.
研究的目的:
- 提供与AD风险相关的已知和新鲜罕见变异的全面概述.
- 突出这些变异在阐明AD病理生理学和确定新药开发途径方面的作用.
- 讨论罕见变异在个人,家庭和人口层面的影响,包括它们在遗传风险预测中的潜力和挑战.
主要方法:
- 对大规模的全外体和基因组测序研究的审查.
- 在全基因组关联研究中改善归算的分析.
- 对专注于研究不足的人群和罕见变异的功能影响的研究进行审查.
主要成果:
- 增加了与AD风险相关的罕见变异的发现,包括TREM2,ABCA7和SORL1.1中的变异.
- 越来越多的研究对这些罕见变异的功能影响进行了测绘.
- 从罕见变体研究中获得的关于AD病原和潜在治疗点的新兴见解.
结论:
- 罕见的变异在阿尔茨海默病的发病过程中起着至关重要的作用,是未来研究的重要领域.
- 了解罕见变异为AD药物开发提供了新的途径,并改善了基因风险预测.
- 对罕见变异的进一步调查对于全面了解AD的遗传结构至关重要.
更多相关视频
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
33.5K
09:38Generalized Psychophysiological Interaction PPI Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
14.8K
相关概念视频
Alzheimer's Disease: Overview
437
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...
437
Human Genetics
528
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
528
Genome-wide Association Studies-GWAS
12.4K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
12.4K
Genetic Lingo
100.1K
Overview
100.1K
Comparing Copy Number Variations and SNPs
17.1K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
17.1K
Alzheimer's Disease: Treatment
158
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...
158
