纵向早期阿尔茨海默病研究队列中的致病变体
Kelly N H Nudelman1,2, Trever Jackson1, Malia Rumbaugh1
1Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
概括
纵向早期阿尔茨海默病研究 (LEADS) 调查了早期认知障碍的遗传原因. 大多数病例以前没有发现致病变体,这表明新的遗传因素与早期发病的阿尔茨海默病有关.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 医学研究 医学研究
背景情况:
- 早发性阿尔茨海默病 (EOAD) 在65岁之前出现,并且具有显著的遗传成分.
- 研究EOAD的遗传因素对于了解疾病机制和开发向疗法至关重要.
- 纵向早期阿尔茨海默病研究 (LEADS) 旨在揭示年轻人认知障碍的遗传基础.
研究的目的:
- 研究LEADS参与者早期认知障碍的遗传病因.
- 查与阿尔茨海默氏症和相关痴呆症相关的基因中的已知致病变体.
- 确定导致早期非AD (EOnonAD) 和早期AD (EOAD) 的新型遗传变异.
主要方法:
- 对299名LEADS参与者 (EOAD和EOnonAD病例) 进行了整体外基因组测序.
- 在关键基因中评估了致病变体的频率:APP,PSEN1,PSEN2,GRN,MAPT和C9ORF72.
- 基因负担测试将LEADS病例与来自帕金森氏症进展标志物倡议 (PPMI) 研究的认知正常对照进行了比较.
主要成果:
- 之前报告的致病变体在1.35%的EOAD和6.58%的EOnonAD病例中被发现.
- 在APP,PSEN1/2,GRN和MAPT中没有观察到罕见的功能变异的显著丰富.
- 鉴定了8种认知障碍病原性变体载体,其中包括PSEN1,GRN,MAPT和C9ORF72.
结论:
- 这些发现表明,LEADS对早期认知障碍的新型遗传致病变体进行了丰富.
- 以前识别的致病变体无法解释LEADS队列中大多数病例.
- LEADS作为未来对早期阿尔茨海默病的遗传研究的宝贵资源.
关键词:
这就是为什么APP APP APP APP.阿尔茨海默病的疾病阿尔茨海默病的疾病.C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9ORF7C9在 GRN GRN GRN 中.马普特 (MAPT) 是一个在PSEN1上.这就是PSEN2的原因.痴呆症 痴呆症是一种痴呆症.这是早期发病的早期发病.遗传学 遗传学 遗传学 是一个测序的测序是指测序的测序.更多相关视频
12:28Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains
Published on: June 3, 2020
17.4K
13:31Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis
Published on: February 12, 2015
8.8K
相关概念视频
Alzheimer's Disease: Overview
506
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...
506
Single Nucleotide Polymorphisms-SNPs
15.2K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.2K
Genome-wide Association Studies-GWAS
13.5K
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...
13.5K
Alzheimer's Disease: Treatment
212
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...
212
