Longitudinal Profiling of Plasma-Derived Glial Extracellular Vesicles in Alzheimer's Disease (GLEVAD)
Longitudinal Profiling of Plasma-Derived Glial Extracellular Vesicles in Alzheimer's Disease: A Focus on the Role of Neuroinflammation and Its Implication for Disease Progression
研究概览
详细说明
The primary goal of the project is to longitudinally profile plasma-derived GDEVs and neuroinflammation biomarkers to better understand their role in AD progression and to investigate novel, non-invasive blood-based biomarkers for improved diagnosis, prognosis, and disease monitoring.
The study will focus on key stages of the AD continuum, investigating the relationship between neuroinflammation and established indicators of core AD pathology, cognitive decline, and clinical progression over time.
An innovative dual translational approach will test the effects of disease-stage-specific GDEVs on healthy human iPSC-derived neurons, assessing their neurotoxic or priming effects and revealing their direct biological impact. This combined approach aims to identify early neuroinflammation signatures and investigate novel diagnostics and therapeutic targets.
A multidisciplinary approach will be adopted to achieve the following four objectives:
Objective 1: To profile changes in plasma-derived GDEV cargo and neuroinflammation biomarkers across the AD continuum, from cognitively normal individuals to those with SCD-AD, MCI-AD and Dem-AD.
Objective 2: To investigate the relationship between GDEVs/neuroinflammation biomarkers and fluid biomarkers of amyloidopathy, tauopathy, and neurodegeneration.
Objective 3: To assess their association with clinical and cognitive markers of AD progression, identifying biological profiles predictive of cognitive decline and clinical progression rate.
Objective 4: To assess the neurotoxic or priming effects of GDEVs from different disease stages on human iPSC-derived neurons from healthy subjects.
研究类型
注册 (估计的)
阶段
- 不适用
联系人和位置
学习联系方式
- 姓名：Guido Maria Giuffrè, PhD
- 电话号码：+390630157936
- 邮箱：guidomaria.giuffre@policlinicogemelli.it
学习地点
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Rome、意大利、00168
- 招聘中
- Fondazione Policlinico Agostino Gemelli IRCCS
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接触：
- Guido Maria Giuffrè, PhD
- 电话号码：+390630154333
- 邮箱：guidomaria.giuffre@policlinicogemelli.it
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- For Ctrl: Individuals with no subjective or objective cognitive complaints, normal performance on standardized neuropsychological assessments, and normal AD biomarkers.
- For SCD-AD: Individuals reporting persistent self-perceived cognitive decline in the absence of objective cognitive impairment on standardized neuropsychological assessments and with preserved functional independence in activities of daily life, with abnormal AD biomarkers
- For MCI-AD: Individuals showing evidence of persistent cognitive decline, either self-reported or observed by an informant, with objective cognitive impairment on standardized neuropsychological assessments and with preserved independence in daily activities, with abnormal AD biomarkers
- For Dem-AD: Individuals with substantial progressive cognitive impairment affecting multiple domains and/or associated neuropsychiatric symptoms, confirmed by objective cognitive impairment on standardized neuropsychological assessments and a clear functional decline impacting independence, abnormal AD biomarkers
- For all subjects: Informed consent form signed by subject or caregiver
Exclusion Criteria:
- Exclusion criteria will be age <55 or >80 years, lack of a reliable study partner, previous or concomitant neurological diseases, major psychiatric disorders, medical conditions potentially able to interfere with cognitive functions, previous participation in experimental studies with amyloid targeting agents, significant systemic inflammatory diseases or use of immunosuppressive medication.
学习计划
研究是如何设计的？
设计细节
- 主要用途：诊断
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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其他：Single Arm
single arm
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blood sampling for plasma biomarkers analyses
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Longitudinal changes
大体时间：24 months
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Longitudinal changes in plasma-derived GDEV cargo and neuroinflammation biomarkers across the Alzheimer's disease continuum
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24 months
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Disease-stage-specific molecular signatures
大体时间：24 months
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Identification of disease-stage-specific GDEV molecular signatures associated with progression along the AD continuum
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24 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Associations between biomarkers
大体时间：24 months
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Identification of associations between GDEV/neuroinflammation biomarkers and established fluid biomarkers of amyloidopathy, tauopathy and neurodegeneration
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24 months
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Relationships with Clinical Measures
大体时间：24 months
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Evaluation of the rate of correlations between plasma GDEV profiles and clinical measures of disease severity, including global cognitive performance, domain-specific cognitive decline, functional impairment and clinical staging (evalauted through neuropsychological assessments and clinical scales)
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24 months
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Predictive Value
大体时间：24 months
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Exploration of the predictive value of baseline and longitudinal GDEV/neuroinflammation profiles in predicting clinical progression along the AD continuum
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24 months
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Neurotoxic or priming effects
大体时间：24 months
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Assessment of the prevalence of neurotoxic or priming effects of GDEVs from different disease stages on human iPSC-derived neurons from healthy subjects, comparing the biological effects of GDEVs across disease stages
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24 months
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合作者和调查者
调查人员
- 首席研究员：Giudo Maria Giuffrè、Fondazione Policlinico Universitario Agostino Gemelli IRCCS
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 27072
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
IPD 计划说明
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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