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Systems Genetics Analysis of Alzheimer's Disease-Related Sleep Loss and the Transition to Dementia

阿尔茨海默氏病相关睡眠不足和向痴呆症转变的系统遗传学分析

基本信息

批准号：
10388971
负责人：
CATHERINE COOK KACZOROWSKI
金额：
$ 88.75万
依托单位：
JACKSON LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-01 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10388971
关键词：
Age Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Amyloid Autopsy Behavior Biological Biological Models Brain Clinical Cognition Cognitive Cognitive aging Cognitive deficits Cohort Studies Communities Complement DNA Data Data Set Dementia Detection Disease Progression Elderly Electroencephalography Gene Targeting Genes Genetic Genetic Variation Genomic Segment Heritability Heterogeneity Human Human Genetics Image Impaired cognition Individual Individual Differences Knowledge Knowledge Portal Late Onset Alzheimer Disease Link Mediating Medical Memory Memory impairment Meta-Analysis Metadata Modeling Molecular Mus Mutation Nerve Degeneration Neurobehavioral Manifestations Outcome Pathology Pathway interactions Patients Phenotype Play Population Predisposition Publications Quality of life Quantitative Trait Loci RNA Research Research Personnel Resources Risk Role Sampling Severity of illness Sleep Sleep Deprivation Sleep Disorders Symptoms System Systems Biology Testing The Jackson Laboratory Translating Translations Validation Variant Visual Work aging gene burden of illness cohort familial Alzheimer disease gene network gene therapy genetic analysis genetic resource genome editing high risk human data human model humanized mouse improved innovation insight machine learning classifier mild cognitive impairment mouse model multidimensional data neuropathology non rapid eye movement novel pre-clinical resilience therapeutically effective tool trait usability

项目摘要

PROJECT SUMMARY Our proposed research is expected to identify genetic factors that underlie disordered sleep associated with Alzheimer's disease (AD), and determine if they are intervenable to stave off cognitive symptoms. Detection and validation of these genes will promote possible treatments through discovery of new targets and biological pathways that may aid in alleviating disease burden and improving quality of life in humans. The data generated in this proposal will also be cross-checked with available datasets from human cohorts and postmortem samples, such that advances in our current understanding of the networks and mechanisms in mice can be understood in the context of human AD. We will leverage advanced mouse models to identify molecular and cellular mechanisms underlying the bidirectional relationship between AD pathology and disruptions in sleep. In Aim 1, we will identify genes and molecular networks associated with sleep loss in a large population of AD mice that better model human AD. In Aim 2, we will translate genes and networks underlying variation in sleep loss to human AD cohorts. Finally, in Aim 3, we will validate genetic and modifiable factors associated with sleep loss and dysfunction, and determine their effects on onset and progression of memory deficits in powerful AD models.

项目总结