Screening ADNI patient cohorts to identify a sub-population that are AD early progressors in validating the prognostic ability of the Alzosure Predict blood test, 6 years in advance of current methods
筛选 ADNI 患者队列,识别 AD 早期进展者亚群,验证 Alzosure Predict 血液检测的预后能力,比现有方法提前 6 年
基本信息
- 批准号:10483271
- 负责人:
- 金额:$ 160.62万
- 依托单位:
- 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:2022-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAffectAgeAge-YearsAgingAlzheimer disease detectionAlzheimer disease preventionAlzheimer disease screeningAlzheimer&aposs DiseaseAlzheimer&aposs disease diagnosisAlzheimer&aposs disease diagnosticAlzheimer&aposs disease testAlzheimer&aposs disease therapyAlzheimer’s disease biomarkerBehavioralBiochemical MarkersBiologicalBiological MarkersBiological ProcessBloodBlood TestsBrainCaringCause of DeathCell CycleCerebrospinal FluidCholinesterase InhibitorsClinicalClinical ResearchCognitionCognitiveCommunitiesConsumptionDementiaDetectionDiabetes MellitusDiagnosisDiagnosticDiagnostic Reagent KitsDiagnostic testsDiseaseDisease ManagementDisease ProgressionEarly DiagnosisEarly treatmentFibroblastsFutureGoalsHomeostasisImpaired cognitionImpairmentIn VitroIndividualInflammationKnowledgeLifeLongitudinal cohortMalignant NeoplasmsMeasuresMedicalMethodsMolecular ConformationN-MethylaspartateNeurodegenerative DisordersNeuronsObesityOutcomeOxidation-ReductionPathogenesisPatient CarePatientsPennsylvaniaPerformancePeripheralPersonal SatisfactionPersonsPlasmaPlayPopulationPredictive ValuePreventionPreventiveProcessPsyche structurePublishingQuality of lifeResearchResearch PersonnelRetrospective cohortRoleSamplingScanningScientistScreening procedureSeverity of illnessSpecificityStagingSymptomsSynapsesTP53 geneTechnology TransferTestingTimeTimeLineTumor SuppressionUnited StatesUniversitiesVariantaccurate diagnosisantagonistbasebrain tissueclinical diagnosisclinical practicecohortcomorbiditycostcost effectivecurative treatmentsdiagnostic biomarkerexperimental studygene functionimprovedminimally invasivenervous system disorderneuroimagingnon-dementedperipheral bloodpredictive testprognosticprognostic valueprotein misfoldingrecruitresearch and developmentscreeningsocioeconomics
项目摘要
ABSTRACT
AD is a progressive dementia with a disease-severity gradient from normal cognition to irreversible cognitive
impairment, and accounts for 60 to 80% of all dementias. There are 10 million new cases per year, and 50 million
total cases worldwide, including 5.8 million people in the United States alone living with AD in 2019. Furthermore,
these figures are expected to significantly escalate in the next decade or two. The AD socioeconomic burden is
substantial; worldwide dementia-related costs increased 35% between 2010 and 2015, and by 2030 are
estimated to reach 2 trillion USD. At present, disease management is symptomatic (cholinesterase inhibitors or
NMDA antagonists) as definitive care options have not yet been established. Given the lack of remedial or
curative therapies for AD, the best option for improving clinical outcomes is early detection and prevention to
enable treatment early-on, maximizing physical, mental, and behavioral wellbeing. Current methods of diagnosis
are time consuming, ambiguous or inconclusive, invasive, and expensive, often requiring advanced cognitive
scanning tests or even requiring examination of the cerebrospinal fluid (CSF) for specific disease biomarkers.
However, evidence suggests AD pathophysiological features occur decades prior to initial symptomatic
presentation, and as such, there is a crucial need for minimally-invasive early disease detection.
The p53 protein plays a well-defined role several diseases as cancer, and its dysregulation also contributes to
comorbidities such as diabetes, obesity, and aging-associated neurodegenerative disorders. Specifically, p53
misfolding/ unfolding (U-p53) was observed in sporadic AD subjects’ peripheral fibroblasts, but was not noted in
age-matched non-AD subjects. The presence of altered p53 in AD pathogenesis is well documented
Based on more than 20 years of R&D and developed by Diadem, AlzoSure Predict is a minimally invasive, cost
effective, blood-based test able to detect U-p53AZ.To address the gap in time and cost-effective early diagnosis
of AD samples as plasma, brain tissue and CSF from individuals at different stages of cognitive decline due to
AD progression and recruited by the well characterized retrospective and longitudinal cohort of ADNI 1,2,3 will
be analyzed by AlzoSure® Predict. The availability and the analysis of different biological samples from the same
individuals will provide additional knowledge about occurrence of the biomarker unfolding process at the brain
and/or systemic level. The main goal is the identification of the subpopulation of early progressing individuals to
AD within the longitudinal cohorts. This will be accomplished in a number of study aims, particularly: Specific
Aim 1, will validate the ability of the biomarker to discriminate the different stage of cognitive decline; Specific
Aim 2, will also allow to establish the specificity of the biomarker toward AD compared to other dementias;
Specific Aim 3 will confirm the clinical utility of the prognostic value of U-p53AZ by categorizing patients into
disease classes and stages; Specific Aim 4 will provide a comparison of the performance of AlzoSure test against
the current diagnostic and prognostic AD methods.
摘要
AD是一种进行性痴呆,其疾病严重程度从正常认知到不可逆转的认知
损害,占所有痴呆的60%至80%。每年有1000万个新病例,5000万个
全球病例总数,包括2019年仅美国就有580万AD患者。此外,
这些数字预计将在未来十年或二十年大幅攀升。AD的社会经济负担是
2010年至2015年,全球与痴呆症相关的成本增加了35%,到2030年
估计将达到2万亿美元。目前,疾病治疗是有症状的(胆碱酯酶抑制剂或
NMDA拮抗剂)作为最终的治疗选择尚未确定。鉴于缺乏补救措施或
治疗阿尔茨海默病,改善临床结果的最佳选择是早期发现和预防
尽早进行治疗,最大限度地提高身体、精神和行为的健康水平。当前的诊断方法
耗时、模棱两可或不确定、侵略性和昂贵,通常需要高级认知
扫描测试,甚至要求对脑脊液(CSF)进行特定疾病生物标志物的检查。
然而,有证据表明,阿尔茨海默病的病理生理特征在最初症状出现前几十年就出现了。
因此,迫切需要微创的早期疾病检测。
P53蛋白在癌症等几种疾病中发挥着明确的作用,它的失调也导致了
糖尿病、肥胖症和衰老相关的神经退行性疾病等共病。具体地说,p53
在散发性AD患者的外周成纤维细胞中观察到错误折叠/去折叠(U-P53),但在
年龄匹配的非AD受试者。阿尔茨海默病发病机制中P53基因改变的存在是有充分证据的
基于20多年的研发,由Diadem开发的AlzoSure Forecast是一种微创、成本
有效的、基于血液的检测能够检测出U-p53AZ。解决了早期诊断在时间和成本上的差距
不同认知减退阶段个体的血浆、脑组织和脑脊液样本
ADNI 1,2,3 Will的回顾和纵向队列特征良好
由AlzoSure®Forecast进行分析。同一样品中不同生物样品的可用性和分析
个人将提供更多关于生物标记物在大脑中展开过程的知识
和/或系统级别。主要目标是确定早期进展个体的亚群,以
AD在纵向队列中。这将通过若干研究目标来实现,特别是:具体
目的1,验证生物标记物区分认知衰退不同阶段的能力;
目的2,还将允许建立与其他痴呆相比的AD的生物标记物的特异性;
具体目标3将确认U-p53AZ的预后价值的临床应用,将患者分为
疾病类别和阶段;特定目标4将提供AlzoSure测试与
目前AD的诊断和预后方法。
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)
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Paul Kinnon其他文献
Paul Kinnon的其他文献
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{{ truncateString('Paul Kinnon', 18)}}的其他基金
Screening ADNI patient cohorts to identify a sub-population that are AD early progressors in validating the prognostic ability of the Alzosure Predict blood test, 6 years in advance of current methods
筛选 ADNI 患者队列,识别 AD 早期进展者亚群,验证 Alzosure Predict 血液检测的预后能力,比现有方法提前 6 年
- 批准号:
10688164 - 财政年份:2022
- 资助金额:
$ 160.62万 - 项目类别:
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