Longitudinal Profiling of Plasma-Derived Glial Extracellular Vesicles in Alzheimer's Disease (GLEVAD)

September 2, 2026 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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

This project aims to longitudinally profile plasma-derived GDEVs and plasma biomarkers of neuroinflammation across three stages of the AD continuum (Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Dementia), exploring their association with biomarkers of amyloidopathy, tauopathy and neurodegeneration, cognitive status and clinical outcome over time. Moreover, GDEVs - collected from subjects at different disease stages - will be used to treat human neurons derived from induced pluripotent stem cells (iPSCs) from healthy controls in order to assess the induced differential neurotoxic or priming effects. This dual translational approach may help identify early pathogenic signatures of neuroinflammation and elucidate their role in disease progression.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Single Arm
single arm
Procedure: blood sampling
blood sampling for plasma biomarkers analyses

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Longitudinal changes
Time Frame: 24 months
Longitudinal changes in plasma-derived GDEV cargo and neuroinflammation biomarkers across the Alzheimer's disease continuum
24 months
Disease-stage-specific molecular signatures
Time Frame: 24 months
Identification of disease-stage-specific GDEV molecular signatures associated with progression along the AD continuum
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Associations between biomarkers
Time Frame: 24 months
Identification of associations between GDEV/neuroinflammation biomarkers and established fluid biomarkers of amyloidopathy, tauopathy and neurodegeneration
24 months
Relationships with Clinical Measures
Time Frame: 24 months
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)
24 months
Predictive Value
Time Frame: 24 months
Exploration of the predictive value of baseline and longitudinal GDEV/neuroinflammation profiles in predicting clinical progression along the AD continuum
24 months
Neurotoxic or priming effects
Time Frame: 24 months
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
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

  • Principal Investigator: Giudo Maria Giuffrè, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2026

Primary Completion (Estimated)

May 18, 2028

Study Completion (Estimated)

May 18, 2028

Study Registration Dates

First Submitted

May 7, 2026

First Submitted That Met QC Criteria

September 2, 2026

First Posted (Actual)

September 3, 2026

Study Record Updates

Last Update Posted (Actual)

September 3, 2026

Last Update Submitted That Met QC Criteria

September 2, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 27072

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Privacy

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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