Understanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer Disease
了解导致阿尔茨海默病神经精神症状的分子机制
基本信息
- 批准号:10450771
- 负责人:
- 金额:$ 183.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-15 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:Adverse effectsAgitationAlzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaAutopsyBiologicalBiological AssayBiological MarkersBiological ModelsBipolar DisorderBrainCaregiver BurdenCell NucleusCellsClinicalClinical TrialsDataData SetDelusionsDementiaDevelopmentDiagnosisDiseaseElectronic Health RecordElementsEnhancersEpigenetic ProcessEpitopesFactor AnalysisGene ExpressionGene Expression ProfileGenesGenetic Enhancer ElementGenetic MarkersGenetic VariationGenomicsGenotypeGoalsHallucinationsHumanImpaired cognitionInstitutionalizationInterventionLeadLinkMachine LearningMajor Depressive DisorderMeasurementMedicineMental DepressionMethodsModelingMolecularNerve DegenerationNuclearOutcomeOutputPathologyPathway interactionsPatientsPatternPersonsPhenotypePrefrontal CortexPrognosisQuality of lifeRegulatory ElementResearchResolutionSamplingSchizophreniaSeveritiesSlideStructureSymptomsTestingTherapeuticTimeTissuesVariantWeightassociated symptombiobankbrain tissuecare giving burdencell typeclinical applicationclinical diagnosisclinical predictorscohortcostdaily functioningdeep learningepigenomeepigenomicsfunctional genomicsgenetic risk factorgenetic variantgenomic datahigh dimensionalityindexinginnovationinterestlearning strategymild cognitive impairmentmolecular markerneuropathologyneuropsychiatric symptomneuropsychiatrynovelnovel therapeuticspatient stratificationphenomicsphenotypic biomarkerpotential biomarkerpredictive modelingprognostic modelsevere mental illnesstherapeutically effectivetraittranscriptometranscriptomicstranslational potential
项目摘要
PROJECT SUMMARY
Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease (AD) and related
dementias that are associated with major adverse effects on daily function and quality of life, and accelerate
time to institutionalization. Of all the NPS, depression is the most frequently observed symptom in people with
mild cognitive impairment and early AD. As the disease progresses, agitation, delusions and hallucinations
become more common, whereas apathy is the most persistent and frequent NPS throughout all the stages of
AD. AD-NPS share some clinical features with serious mental illnesses (SMIs), such as schizophrenia, bipolar
disorder and major depressive disorder, but whether these conditions share similar aethiopathies is unclear.
Given that reliable treatments for NPS in the context of AD and other dementias do not exist, a better
understanding of the molecular mechanisms and pathways underlying NPS in AD and other neuropsychiatric
illnesses is a critical next step to identify reliable biomarkers that could lead to novel therapeutics.
There are two overarching goals of this proposal. First, we will identify the molecular mechanisms
and neuropathological changes that are associated with the presence of NPS in patients with AD. Second, we
will examine if the mechanisms of pathology associated with NPS are shared or distinct among AD and SMIs.
More specifically, we propose to build multi-scale integrative models using phenomics and genomics data from
1,264 autopsy cases derived from a single brain bank. The bank includes detailed phenomics data such as
well characterized NPS, clinical diagnosis (AD and other neurodegenerative or neuropsychiatric traits), severity
of cognitive decline and neuropathology for each patient sample. From each case, we will apply innovative
approaches that reduce the cost and technical biases associated with conventional methods, and capture gene
expression signatures and epigenetic regulatory elements at the single-cell level. Novel deep-learning methods
will be applied for the multi-scale integration of neuropathologic changes with genetic markers and functional
genomic changes (such as changes in gene expression and enhancer sequences) within specific cell types, to
predict various NPS in AD and other neuropsychiatric traits; we refer to these integrative models as genotype-
marker-phenotype models. We expect that these models will enable us to assign genotypes and molecular
markers to specific NPS within AD and other neuropsychiatric traits at the single-cell level, an unprecedented
level of resolution. In addition, we will test the translational potential of the genotype-marker-phenotype models
to predict AD-NPS using independent large-scale biobank datasets, in which genotypes and electronic health
records are available. Successful completion of the proposed studies will have immediate utility by generating
potential biomarkers for NPS diagnosis and prognosis and by providing predictive models for patient
stratification in clinical trials. In the longer term, our models will help us create a blueprint for therapeutic
strategies and interventions to treat NPS in AD.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
STEVEN M FINKBEINER其他文献
STEVEN M FINKBEINER的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('STEVEN M FINKBEINER', 18)}}的其他基金
Image Tools for Computational Cellular Barcoding and Automated Annotation
用于计算细胞条形码和自动注释的图像工具
- 批准号:
10552638 - 财政年份:2022
- 资助金额:
$ 183.32万 - 项目类别:
Image Tools for Computational Cellular Barcoding and Automated Annotation
用于计算细胞条形码和自动注释的图像工具
- 批准号:
10367874 - 财政年份:2022
- 资助金额:
$ 183.32万 - 项目类别:
Role of central and peripheral immune crosstalk in FTD-Grn neurodegeneration
中枢和外周免疫串扰在 FTD-Grn 神经变性中的作用
- 批准号:
10514263 - 财政年份:2022
- 资助金额:
$ 183.32万 - 项目类别:
Cell and Network Disruptions and Associated Pathogenenesis in Tauopathy and Down Syndrome
Tau 蛋白病和唐氏综合症的细胞和网络破坏及相关发病机制
- 批准号:
9974319 - 财政年份:2020
- 资助金额:
$ 183.32万 - 项目类别:
Cell and Network Disruptions and Associated Pathogenenesis in Tauopathy and Down Syndrome
Tau 蛋白病和唐氏综合症的细胞和网络破坏及相关发病机制
- 批准号:
10377486 - 财政年份:2020
- 资助金额:
$ 183.32万 - 项目类别:
Cell and Network Disruptions and Associated Pathogenenesis in Tauopathy and Down Syndrome
Tau 蛋白病和唐氏综合症的细胞和网络破坏及相关发病机制
- 批准号:
10601035 - 财政年份:2020
- 资助金额:
$ 183.32万 - 项目类别:
Cell and Network Disruptions and Associated Pathogenenesis in Tauopathy and Down Syndrome
Tau 蛋白病和唐氏综合症的细胞和网络破坏及相关发病机制
- 批准号:
10599756 - 财政年份:2020
- 资助金额:
$ 183.32万 - 项目类别:
Understanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer Disease
了解导致阿尔茨海默病神经精神症状的分子机制
- 批准号:
10406707 - 财政年份:2019
- 资助金额:
$ 183.32万 - 项目类别:
Understanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer Disease
了解导致阿尔茨海默病神经精神症状的分子机制
- 批准号:
10651757 - 财政年份:2019
- 资助金额:
$ 183.32万 - 项目类别:
Understanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer Disease
了解导致阿尔茨海默病神经精神症状的分子机制
- 批准号:
10439255 - 财政年份:2019
- 资助金额:
$ 183.32万 - 项目类别:
相似海外基金
Relationship between Biomarkers of Oxidative Stress and Agitation Severity in Moderate-to-severe Alzheimer's Disease
中重度阿尔茨海默病氧化应激生物标志物与躁动严重程度之间的关系
- 批准号:
497994 - 财政年份:2023
- 资助金额:
$ 183.32万 - 项目类别:
Effects of dexmedetomidine on agitation in critically ill TBI patients - DEX-TBI
右美托咪定对危重 TBI 患者躁动的影响 - DEX-TBI
- 批准号:
488402 - 财政年份:2023
- 资助金额:
$ 183.32万 - 项目类别:
Operating Grants
Co-design and evaluation of sensor-instrumented ‘smart socks’ (MPATIX) to improve management of distress and agitation for people with dementia
共同设计和评估传感器仪表“智能袜子”(MPATIX),以改善痴呆症患者的痛苦和躁动管理
- 批准号:
10055596 - 财政年份:2023
- 资助金额:
$ 183.32万 - 项目类别:
Collaborative R&D
Identifying pre-agitation biometric signature in dementia patients: A feasibility study
识别痴呆症患者的躁动前生物识别特征:可行性研究
- 批准号:
486612 - 财政年份:2022
- 资助金额:
$ 183.32万 - 项目类别:
Studentship Programs
Relationship between 4-Hydroxynonenal and Agitation Severity in Alzheimer’s Disease
4-羟基壬烯醛与阿尔茨海默病患者躁动严重程度之间的关系
- 批准号:
486589 - 财政年份:2022
- 资助金额:
$ 183.32万 - 项目类别:
Studentship Programs
Agitation in Alzheimer's Disease: Identification and Prediction Using Digital Behavioral Markers and Indoor Environmental Factors
阿尔茨海默病中的躁动:使用数字行为标记和室内环境因素进行识别和预测
- 批准号:
10404523 - 财政年份:2021
- 资助金额:
$ 183.32万 - 项目类别:
Clinical Decision Support Tool to Assess Risk and Prevent Agitation Events
用于评估风险和预防躁动事件的临床决策支持工具
- 批准号:
10683499 - 财政年份:2021
- 资助金额:
$ 183.32万 - 项目类别:
Development of Memesto, a wearable repetitive message and music therapy device that senses and reduces agitation in persons with AD/ADRD.
开发 Memesto,一种可穿戴式重复信息和音乐治疗设备,可感知并减少 AD/ADRD 患者的躁动。
- 批准号:
10322846 - 财政年份:2021
- 资助金额:
$ 183.32万 - 项目类别:
Agitation in Alzheimer's Disease: Identification and Prediction Using Digital Behavioral Markers and Indoor Environmental Factors
阿尔茨海默病中的躁动:使用数字行为标记和室内环境因素进行识别和预测
- 批准号:
10190522 - 财政年份:2021
- 资助金额:
$ 183.32万 - 项目类别:
Clinical Decision Support Tool to Assess Risk and Prevent Agitation Events
用于评估风险和预防躁动事件的临床决策支持工具
- 批准号:
10365272 - 财政年份:2021
- 资助金额:
$ 183.32万 - 项目类别:














{{item.name}}会员




