Peripheral Biomarkers for Early Diagnosis of Mixed Pathologies in AD/ADRD
用于 AD/ADRD 混合病理早期诊断的外周生物标志物
基本信息
- 批准号:10669877
- 负责人:
- 金额:$ 75.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-01 至 2028-02-29
- 项目状态:未结题
- 来源:
- 关键词:AffectAgeAlzheimer&aposs DiseaseAlzheimer&aposs disease diagnosisAlzheimer&aposs disease patientAlzheimer&aposs disease related dementiaAmyloid beta-ProteinAutopsyBiological AssayBiological MarkersBiopsyBiopsy SpecimenBrainBrain imagingCadaverClinicClinicalCollectionConsensusDementiaDementia with Lewy BodiesDepositionDetectionDevelopmentDiagnosisDiagnostic testsDifferential DiagnosisDiseaseDisease ProgressionEarly DiagnosisEmerging TechnologiesGoalsImmunoassayLewy Body DementiaMeasuresMemoryOutcomeOutcome StudyParkinson DiseaseParkinson&aposs DementiaParticipantPathologicPathologyPatient CarePatientsPeripheralPersonsPositioning AttributeProbabilityProgressive Supranuclear PalsyRegistriesResearchResourcesSamplingSeverity of illnessSkinSpecimenSymptomsTauopathiesTestingTimeValidationVisitaccurate diagnosisalpha synucleinbiobankbrain tissueclinical diagnosisclinical practicecomorbiditycorticobasal degenerationcorticobasal syndromediagnostic assaydiagnostic biomarkerdiagnostic toolearly detection biomarkersfollow-upillness lengthimprovedneuropathologynew technologynovel markerprion-likeprospectiveprotein aggregationrecruitsexsuccesssynucleinopathytau Proteinstau aggregationtau-1therapeutic development
项目摘要
The overall goal of our proposed research is to develop robust premortem biomarkers for accurate and
differential diagnosis of Alzheimer's disease (AD), non-AD tauopathies, Lewy body dementia (LBD), and their
comorbidities. A pathological hallmark of AD and other tauopathies is the deposition of tau protein aggregates
in the brain, whereas in LBD there is accumulation of α-synuclein (aSyn) aggregates. Strikingly, more than half
of patients with clinically diagnosed AD or LBD have concomitant tau and aSyn co-pathologies at autopsy.
Moreover, patients with mixed tau and aSyn pathologies often suffer from worse clinical outcomes. Currently, it
is highly challenging to clinically differentiate AD, LBD, and mixed AD/LBD due to overlapping symptoms.
Moreover, co-existence of aSyn pathology also occurs frequently in non-AD tauopathies. Recent advances in
brain imaging and immunoassays of amyloid-β and phosphorylated tau (p-tau) have greatly facilitated diagnosis
of typical AD. However, these assays fail to identify non-AD tauopathies and mixed AD/LBD. Therefore,
alternative measures in easily accessible biospecimens are warranted, especially if they enable simultaneous
detection of tau and aSyn aggregates in patients with mixed tauopathies and synucleinopathies. In preliminary
studies, we have leveraged the newly emerged technology known as the real-time quaking-induced conversion
assay (tau RT-QuIC) for specific detection of tau aggregates in the skin of patients with AD and non-AD
tauopathies. In conjunction with recently established aSyn RT-QuIC, we are in a unique position to accurately
diagnose patients with mixed tau and aSyn pathologies using easily accessible skin specimens. We hypothesize
that skin tau and aSyn detected by RT-QuIC are novel biomarkers for early and differential diagnosis of
mixed tauopathies/synucleinopathies in routine clinical practice. We propose to test this hypothesis by
pursuing three Aims: 1) Establish dual skin RT-QuIC biomarker assays for mixed tauopathies/synucleinopathies
using neuropathologically confirmed cases; 2) Assess skin tau and aSyn detected by RT-QuIC as reliable
biomarkers for premortem diagnosis of mixed tauopathies and synucleinopathies; and 3) Evaluate skin tau/aSyn
biomarker assays for improving the differential diagnosis of mixed tauopathies/synucleinopathies through
longitudinal follow-up. This translational project is supported by rich clinical resources and a strong team of basic
and clinical neuroscientists. The successful outcome of our proposal will establish a robust skin-based diagnostic
test for mixed pathologies that is prevalent in AD and related dementias, thus facilitating better patient care and
development of disease-modifying therapies.
我们提出的研究的总体目标是开发强大的死前生物标志物,以实现准确和
阿尔茨海默病 (AD)、非 AD tau蛋白病、路易体痴呆 (LBD) 及其相关疾病的鉴别诊断
AD 和其他 tau 病的病理特征是 tau 蛋白聚集体的沉积。
在大脑中,而在 LBD 中,α-突触核蛋白 (aSyn) 聚集体聚集,超过一半。
临床诊断的 AD 或 LBD 患者在尸检时伴有 tau 和 aSyn 共同病理。
此外,目前,患有混合 tau 和 aSyn 病理的患者通常会遭受更差的临床结果。
由于症状重叠,临床区分 AD、LBD 和混合型 AD/LBD 极具挑战性。
此外,aSyn 病理学的共存也经常发生在非 AD tau蛋白病中。
β-淀粉样蛋白和磷酸化 tau (p-tau) 的脑成像和免疫分析极大地促进了诊断
然而,这些检测无法识别非 AD tau蛋白病和混合 AD/LBD。
在易于获取的生物样本中采取替代措施是必要的,特别是如果它们能够同时进行
初步检测混合型 tau 蛋白病和突触核蛋白病患者中的 tau 蛋白和 aSyn 聚集体。
研究中,我们利用了称为实时地震诱导转换的新兴技术
用于特异性检测 AD 和非 AD 患者皮肤中 tau 聚集体的测定 (tau RT-QuIC)
结合最近建立的 aSyn RT-QuIC,我们处于独特的地位,可以准确地
使用易于获取的皮肤标本诊断患有混合 tau 和 aSyn 病理的患者。
RT-QuIC 检测到的皮肤 tau 和 aSyn 是用于早期和鉴别诊断的新型生物标志物
我们建议通过常规临床实践来检验这一假设。
追求三个目标:1) 建立针对混合 tau蛋白病/突触核蛋白病的双皮肤 RT-QuIC 生物标志物检测
使用神经病理学确诊的病例;2) 评估 RT-QuIC 检测到的皮肤 tau 和 aSyn 的可靠性
用于死前诊断混合 tau 病和突触核蛋白病的生物标志物;以及 3) 评估皮肤 tau/aSyn
通过生物标志物测定改善混合 tau蛋白病/突触核蛋白病的鉴别诊断
该转化项目有丰富的临床资源和强大的基础团队支持。
我们的建议的成功结果将建立一个强大的基于皮肤的诊断。
测试 AD 和相关痴呆症中常见的混合病理,从而促进更好的患者护理和
疾病修饰疗法的开发。
项目成果
期刊论文数量(0)
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{{ truncateString('SHU G. CHEN', 18)}}的其他基金
Skin biomarkers for diagnosing and characterizing AD and ADRD
用于诊断和表征 AD 和 ADRD 的皮肤生物标志物
- 批准号:
10491802 - 财政年份:2021
- 资助金额:
$ 75.6万 - 项目类别:
Skin biomarkers for diagnosing and characterizing AD and ADRD
用于诊断和表征 AD 和 ADRD 的皮肤生物标志物
- 批准号:
10307911 - 财政年份:2021
- 资助金额:
$ 75.6万 - 项目类别:
Skin biomarkers for diagnosing and characterizing AD and ADRD
用于诊断和表征 AD 和 ADRD 的皮肤生物标志物
- 批准号:
10673714 - 财政年份:2021
- 资助金额:
$ 75.6万 - 项目类别:
Peripheral Tissue Biomarker for Premortem Diagnosis of Lewy Body Dementia
用于路易体痴呆死前诊断的外周组织生物标志物
- 批准号:
10705299 - 财政年份:2021
- 资助金额:
$ 75.6万 - 项目类别:
Peripheral Tissue Biomarker for Premortem Diagnosis of Lewy Body Dementia
用于路易体痴呆死前诊断的外周组织生物标志物
- 批准号:
10653599 - 财政年份:2021
- 资助金额:
$ 75.6万 - 项目类别:
Peripheral Tissue Biomarker for Premortem Diagnosis of Lewy Body Dementia
用于路易体痴呆死前诊断的外周组织生物标志物
- 批准号:
10248548 - 财政年份:2020
- 资助金额:
$ 75.6万 - 项目类别:
Peripheral Tissue Biomarker for Premorten Diagnosis of Lewy Body Dementia
用于路易体痴呆临终诊断的外周组织生物标志物
- 批准号:
10401974 - 财政年份:2020
- 资助金额:
$ 75.6万 - 项目类别:
Peripheral Tissue Biomarker for Premortem Diagnosis of Lewy Body Dementia
用于路易体痴呆死前诊断的外周组织生物标志物
- 批准号:
10064737 - 财政年份:2020
- 资助金额:
$ 75.6万 - 项目类别:
Assessing skin biomarkers for preclinical diagnosis of PD and non-PD Parkinsonism
评估皮肤生物标志物用于帕金森病和非帕金森病的临床前诊断
- 批准号:
10256807 - 财政年份:2019
- 资助金额:
$ 75.6万 - 项目类别:
Assessing skin biomarkers for preclinical diagnosis of PD and non-PD Parkinsonism
评估皮肤生物标志物用于帕金森病和非帕金森病的临床前诊断
- 批准号:
10622565 - 财政年份:2019
- 资助金额:
$ 75.6万 - 项目类别:
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