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
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Guido Maria Giuffrè, PhD
- 電話番号：+390630157936
- メール：guidomaria.giuffre@policlinicogemelli.it
研究場所
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Rome、イタリア、00168
- 募集
- Fondazione Policlinico Agostino Gemelli IRCCS
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コンタクト：
- Guido Maria Giuffrè, PhD
- 電話番号：+390630154333
- メール：guidomaria.giuffre@policlinicogemelli.it
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-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：診断
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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他の：Single Arm
single arm
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blood sampling for plasma biomarkers analyses
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Longitudinal changes
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Associations between biomarkers
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
捜査官
- 主任研究者：Giudo Maria Giuffrè、Fondazione Policlinico Universitario Agostino Gemelli IRCCS
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 27072
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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