DementiasRF-2021-123742NCT07207486
In-depth Analysis of Cholesterol Metabolism and Related Biomarkers in the Pathogenesis and Progression of the Disease in Neurodegenerative Dementias
An observational study of Dementias and Neurodegenerative Dementia, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 2 sites in Italy.
Trial summary
The aim of the study is to evaluate the role of cholesterol in the pathogenesis of neurodegenerative dementias. Hypercholesterolemia is a known risk factor for Alzheimer disease (AD), and oxysterols, the principal cholesterol metabolites, are involved in neuroinflammation, amyloid aggregation, and tau accumulation. Read more about this study
- Who is it for?
- Ages 40 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Dementias, Neurodegenerative Dementia
- How many people
- 80 participants
- Where
- 2 sitesItaly
- Study dates
- 5 Jun 2023to 29 Apr 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: We will use samples (CSF and plasma) already collected from patients from Unit 1 over years. We will include 40 AD, 40 FTD and 20 age-matched non demented controls. Clinical and MRI data will be retrospectively collected as well as the levels of markers of neurodegeneration (tau, Abeta42 and phospho-tau) on CSF. Longitudinal study We will recruit 30 AD patients, 20 FTD patients and 10 patients with primary tauopathies (PSP/CBD) from out and inpatients of Neurology 5-Neuropathology Unit. A group of 20 age-matched subjects without neurological and/or psychiatric diseases will be enrolled as controls. The duration of enrolment will be 18 months.
Who may be able to join
- Age 40-85
- Diagnosis based on the current diagnostic criteria for AD (McKhann et al., 2011), FTD (Gorno-Tempini et al., 2011; Rascovsky et al., 2011), PSP and CBD (Amstrong et al., 2013; Höglinger et al., 2017)
- Mini Mental State Examination MMSE > 10.
Who cannot join
- Other neurological or psychiatric disorders Severe chronic metabolic diseases
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy2 sites, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, 20133
Paola Caroppo, MD, 02.2394.2260, paola.caroppo@istituto-besta.it
Aurora Romeo, 02.2394.2260, aurora.romeo@istituto-besta.it
- Withdrawn
Università di Torino AOU San Luigi Gonzaga
Torino, to, 10043
About this study
The aim of the study is to evaluate the role of cholesterol in the pathogenesis of neurodegenerative dementias. Hypercholesterolemia is a known risk factor for Alzheimer disease (AD), and oxysterols, the principal cholesterol metabolites, are involved in neuroinflammation, amyloid aggregation, and tau accumulation.
Oxysterols will be measured in different biological samples (post-mortem brain tissue, CSF, and plasma) from patients with different neurodegenerative dementias, including AD, frontotemporal dementia (FTD), and primary tauopathies. This approach will allow determination of whether their modifications correlate primarily with Aß deposition, tauopathy, or neuronal loss, with the goal of identifying correlations with disease severity and progression.
Since preliminary results suggest that the levels of most oxysterols in the brain significantly increase in parallel with the levels of the enzyme PCSK9, the investigators will explore the role of cholesterol metabolism and PCSK9 in AD and other dementias to evaluate whether cholesterol dysregulation represents a common alteration across these neurodegenerative disorders or is specific to AD
Read the detailed description
The project is a monocentric retrospective and prospective low-intervention clinical study. All samples collected will be sent for analysis to the Laboratory of General Pathology and Pathophysiology, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano (TO), Italy.
- Selection and characterization of post-mortem brains Twenty brains from patients with AD (ranging from Braak stage II to VI of neurofibrillary pathology severity), ten brains from patients with FTD/tauopathies, and six brains from FTD/TDP43 patients will be included in the study. These samples are already available for the project and have been neuropathologically characterized by Neurology 5 - Neuropathology Unit.
- Recruitment and follow-up of patients with neurodegenerative dementias Retrospective study Samples (CSF and plasma) previously collected from patients at Neurology 5 - Neuropathology Unit over the years will be used. The study will include 40 AD patients, 40 FTD patients, and 20 age-matched non-demented controls. Clinical and MRI data will be retrospectively collected, as well as levels of markers of neurodegeneration (tau, Abeta42, and phospho-tau) in CSF. Longitudinal study During the first 18 months of the project, 30 AD patients, 20 FTD patients, and 10 patients with primary tauopathies (PSP/CBD) will be recruited. A group of 20 age-matched healthy subjects will serve as controls. All patients and controls will undergo a comprehensive neurologic assessment, a neuropsychological evaluation, and a brain MRI with a standard protocol at baseline (T0) and after 1 year (T1). CSF collection will be performed at baseline in patients. DNA and plasma will be collected from controls and patients at baseline and follow-up. Measurements of BMI, total cholesterol, LDL and HDL cholesterol, and triglycerides will be performed at baseline and follow-up in all subjects. ApoE genotype will be analyzed for all subjects to determine E2, E3, and E4 polymorphisms. MRI will be performed on a 3T scanner, including volumetric T1, FLAIR, T2, DWI, and DTI sequences at baseline and follow-up.
- Study of the role of the enzyme PCSK9 in the brain (performed by University of Turin) SK-N-BE cells and mouse-derived primary cortical neurons and astrocytes will be treated with PCSK9 or with an oxysterol mixture obtained from brain dosages.
- Conditions
- Dementias, Neurodegenerative Dementia
- Keywords
- Cholesterol metabolism, Neurodegenerative dementias
- Medical subject headings
- Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| AD | Patient with Alzheimer's disease | |
| FTD | Patient wirh Frontotemporal dementia | |
| PSP/CBD | Patient with tauopathy | |
| CN | Controll subjects |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterize differences in cholesterol precursors
To identify and characterize differences in cholesterol precursors and metabolites between patients with neurodegenerative dementias vs controls and between patients with different types of neurodegenerative dementia.
Measured: 12 months
Secondary outcomes (7)
different brain areas
To identify and characterize different levels of cholesterol precursors and metabolites as well as lipidomics and metabolomics changes in different brain areas of the same patients categorized as involved or spared by the different types of pathological changes.
Measured: 12 months
cerebral oxysterol changes in AD
To find out whether cerebral oxysterol changes in AD (see preliminary results) involve globally the brain suggesting a general derangement of cerebral cholesterol metabolism or selectively brain areas involved by specific primary (Abeta deposition, tauopathy) or secondary (astrogliosis, microglial activation, neuroinflammation) alterations
Measured: 12 months
different cholesterol precursors in neurodegenerative diseases examined in CSF and plasma
To identify different levels of cholesterol precursors and metabolites as well as lipidomics and metabolomics changes at different stages of the different neurodegenerative diseases examined in CSF and plasma.
Measured: 12 months
cortical atrophy
To ascertain whether correlations exist between cholesterol precursors and metabolites abnormalities, severity of the disease, cortical atrophy, glial and microglial reactive changes and neuroinflammation in neurodegenerative dementias.
Measured: 12 months
PCSK9
To verify whether changes in the levels of PCSK9 and other cholesterol metabolism-related proteins are present in patients with the neurodegenerative dementias (brain tissue, CSF, and plasma).
Measured: 12 months
PCSK9 in neurons
Levels of inflammatory markers and neurodegeneration-related proteins in neurons and astrocytes after treatment with PCSK9 in vitro.
Measured: 12 months
potential neurotoxic action of PCSK9
Efficacy of the new nanoparticle (NPs) formulation carrying anti-PCSK9 antibody in reducing PCSK9-induced neurotoxicity in neuronal and astrocyte cultures in vitro.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2025
- Study start5 Jun 2023
- Primary completion29 Apr 2027 (estimated)
- Study completion29 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DementiasStudies of the same condition, open and under way.
- More trials run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Università di Torino, Torino, San Luigi Gonzaga Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07207486
- Sponsor's protocol ID
- RF-2021-12374277
- Acronym
- RF-2021-123742
- Status last verified
- Nov 2026
- First submitted
- 26 Sep 2025
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In-depth Analysis of Cholesterol Metabolism and Related Biomarkers in the Pathogenesis and Progression of the Disease in Neurodegenerative Dementias
- ClinicalTrials.gov ID
- NCT07207486
- Acronym / sponsor ID
- RF-2021-123742 / RF-2021-12374277
- Conditions
- Dementias, Neurodegenerative Dementia
- Keywords
- Cholesterol metabolism, Neurodegenerative dementias
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaUniversity, hospital or other
- Collaborators
- Università di Torino, Torino, San Luigi Gonzaga Hospital
- Study start
- 5 Jun 2023 (actual)
- Primary completion
- 29 Apr 2027 (estimated)
- Study completion
- 29 Apr 2027 (estimated)
- First posted
- 6 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to evaluate the role of cholesterol in the pathogenesis of neurodegenerative dementias. Hypercholesterolemia is a known risk factor for Alzheimer disease (AD), and oxysterols, the principal cholesterol metabolites, are involved in neuroinflammation, amyloid aggregation, and tau accumulation.
Oxysterols will be measured in different biological samples (post-mortem brain tissue, CSF, and plasma) from patients with different neurodegenerative dementias, including AD, frontotemporal dementia (FTD), and primary tauopathies. This approach will allow determination of whether their modifications correlate primarily with Aß deposition, tauopathy, or neuronal loss, with the goal of identifying correlations with disease severity and progression.
Since preliminary results suggest that the levels of most oxysterols in the brain significantly increase in parallel with the levels of the enzyme PCSK9, the investigators will explore the role of cholesterol metabolism and PCSK9 in AD and other dementias to evaluate whether cholesterol dysregulation represents a common alteration across these neurodegenerative disorders or is specific to AD
Detailed description
The project is a monocentric retrospective and prospective low-intervention clinical study. All samples collected will be sent for analysis to the Laboratory of General Pathology and Pathophysiology, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano (TO), Italy.
- Selection and characterization of post-mortem brains Twenty brains from patients with AD (ranging from Braak stage II to VI of neurofibrillary pathology severity), ten brains from patients with FTD/tauopathies, and six brains from FTD/TDP43 patients will be included in the study. These samples are already available for the project and have been neuropathologically characterized by Neurology 5 - Neuropathology Unit.
- Recruitment and follow-up of patients with neurodegenerative dementias Retrospective study Samples (CSF and plasma) previously collected from patients at Neurology 5 - Neuropathology Unit over the years will be used. The study will include 40 AD patients, 40 FTD patients, and 20 age-matched non-demented controls. Clinical and MRI data will be retrospectively collected, as well as levels of markers of neurodegeneration (tau, Abeta42, and phospho-tau) in CSF. Longitudinal study During the first 18 months of the project, 30 AD patients, 20 FTD patients, and 10 patients with primary tauopathies (PSP/CBD) will be recruited. A group of 20 age-matched healthy subjects will serve as controls. All patients and controls will undergo a comprehensive neurologic assessment, a neuropsychological evaluation, and a brain MRI with a standard protocol at baseline (T0) and after 1 year (T1). CSF collection will be performed at baseline in patients. DNA and plasma will be collected from controls and patients at baseline and follow-up. Measurements of BMI, total cholesterol, LDL and HDL cholesterol, and triglycerides will be performed at baseline and follow-up in all subjects. ApoE genotype will be analyzed for all subjects to determine E2, E3, and E4 polymorphisms. MRI will be performed on a 3T scanner, including volumetric T1, FLAIR, T2, DWI, and DTI sequences at baseline and follow-up.
- Study of the role of the enzyme PCSK9 in the brain (performed by University of Turin) SK-N-BE cells and mouse-derived primary cortical neurons and astrocytes will be treated with PCSK9 or with an oxysterol mixture obtained from brain dosages.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| AD | – | –Patient with Alzheimer's disease |
| FTD | – | –Patient wirh Frontotemporal dementia |
| PSP/CBD | – | –Patient with tauopathy |
| CN | – | –Controll subjects |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- We will use samples (CSF and plasma) already collected from patients from Unit 1 over years. We will include 40 AD, 40 FTD and 20 age-matched non demented controls. Clinical and MRI data will be retrospectively collected as well as the levels of markers of neurodegeneration (tau, Abeta42 and phospho-tau) on CSF. Longitudinal study We will recruit 30 AD patients, 20 FTD patients and 10 patients with primary tauopathies (PSP/CBD) from out and inpatients of Neurology 5-Neuropathology Unit. A group of 20 age-matched subjects without neurological and/or psychiatric diseases will be enrolled as controls. The duration of enrolment will be 18 months.
Key inclusion criteria (3 listed)
- Age 40-85
- Diagnosis based on the current diagnostic criteria for AD (McKhann et al., 2011), FTD (Gorno-Tempini et al., 2011; Rascovsky et al., 2011), PSP and CBD (Amstrong et al., 2013; Höglinger et al., 2017)
- Mini Mental State Examination MMSE > 10.
Key exclusion criteria (1 listed)
- Other neurological or psychiatric disorders Severe chronic metabolic diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Characterize differences in cholesterol precursors
Time frame: 12 months
To identify and characterize differences in cholesterol precursors and metabolites between patients with neurodegenerative dementias vs controls and between patients with different types of neurodegenerative dementia.
7 secondary outcomes
different brain areas
Time frame: 12 months
cerebral oxysterol changes in AD
Time frame: 12 months
different cholesterol precursors in neurodegenerative diseases examined in CSF and plasma
Time frame: 12 months
cortical atrophy
Time frame: 12 months
PCSK9
Time frame: 12 months
PCSK9 in neurons
Time frame: 12 months
potential neurotoxic action of PCSK9
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dementias and Neurodegenerative Dementia, run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Paola Caroppo, MD (02.2394.2260 ext. 2260, paola.caroppo@istituto-besta.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterize differences in cholesterol precursors (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.