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The Stanford Extreme Phenotypes in Alzheimer's Disease (StEP AD) Cohort

斯坦福阿尔茨海默病极端表型 (StEP AD) 队列

基本信息

批准号：
10431761
负责人：
Michael D Greicius
金额：
$ 24.37万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10431761
关键词：
Affect Age Alleles Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Alzheimer&apos s disease risk American Amyloid Amyloid beta-Protein Precursor Apolipoprotein E Autopsy Biological Biological Assay Brain Diseases Brain imaging Categories Cerebrospinal Fluid Cognitive Databases Disease Early Onset Alzheimer Disease Genes Genetic Genetic Diseases Genetic Risk Goals Heritability Immunophenotyping Induced pluripotent stem cell derived neurons Lead Molecular Neurodegenerative Disorders Neurons Participant Pathogenesis Pathway interactions Patients Persons Phenotype Positron-Emission Tomography Proteomics Research Research Personnel Resources Sampling Single Nucleotide Polymorphism Source Twin Studies Universities Variant autosomal dominant mutation base brain tissue causal variant cohort design disorder risk drug development early onset exome exome sequencing expectation falls gene discovery genetic risk factor genetic variant genome wide association study high risk innovation insight new therapeutic target novel phenotypic data presenilin-1 presenilin-2 rare variant recruit resilience targeted sequencing

项目摘要

Project Summary/Abstract Alzheimer's disease (AD) is a common, progressive, and ultimately fatal brain disease. Currently approved treatments provide only minimal symptomatic benefits and do not stop the disease from progressing. The field is in dire need of novel drug targets which could lead to disease-modifying therapies. The most common genetic risk factor for AD is the ε4 variant of the apolipoprotein E gene (APOE4). The current study will take advantage of the strong effect of APOE4 to discover new genetic variants that either increase risk for AD or reduce risk for AD. The research team—based at Stanford University but including collaborators at 13 other research centers—will recruit and study participants that fall into one two rare categories: cognitively normal people carrying one or two copies of the high risk APOE4 gene (protected APOE4 carriers) and young patients who early-onset AD (EOAD) before age 65 despite not carrying APOE4 gene. These subjects, the Stanford Extreme Phenotypes in AD (StEP AD) cohort, will undergo whole-exome sequencing and their exomes will be combined with large, publicly available exomes from ~4500 healthy older controls and ~5000 AD patients. In Aim 1 the research team will look for rare genetic variants seen more often in protected APOE4 carriers than in AD patients. In Aim 2 the team will look for rare genetic variants seen in APOE4-negative EOAD patients but not in healthy older controls. Most of the StEP AD cohort will undergo “deep phenotyping” to include structural and molecular brain imaging, spinal fluid analysis, immunophenotyping, and culturing of participant-specific neurons. In Aim 3, the deep phenotyping data will be used to begin to understand the molecular effects of the rare protective or causal genetic variants identified in Aims 1 and 2. Rare but powerful genetic variants identified and characterized in this study will provide novel drug targets for the design of potentially disease- modifying treatments.

项目总结/文摘

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Confirming Pathogenicity of the F386L PSEN1 Variant in a South Asian Family With Early-Onset Alzheimer Disease.

DOI：
10.1212/nxg.0000000000000647
发表时间：
2022-03
期刊：
Neurology. Genetics
影响因子：
0
作者：
Eger SJ;Le Guen Y;Khan RR;Hall JN;Kennedy G;Zaharchuk G;Couthouis J;Brooks WS;Velakoulis D;Napolioni V;Belloy ME;Dalgard CL;Mormino EC;Gitler AD;Greicius MD
通讯作者：
Greicius MD