In-depth Analysis of Cholesterol Metabolism and Related Biomarkers in the Pathogenesis and Progression of the Disease in Neurodegenerative Dementias

NCT07207486 | Recruiting

• 1 other identifier: RF-2021-12374277
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 2

Brief 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. 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

Conditions

Dementias; Neurodegenerative Dementia

Keywords

Cholesterol metabolism; Neurodegenerative dementias

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (7)

• different brain areas

  12 months

• cerebral oxysterol changes in AD

  12 months

• different cholesterol precursors in neurodegenerative diseases examined in CSF and plasma

  12 months

• cortical atrophy

  12 months

• PCSK9

  12 months

Study Arms (4)

AD

Patient with Alzheimer's disease

FTD

Patient wirh Frontotemporal dementia

PSP/CBD

Patient with tauopathy

CN

Controll subjects

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• Other neurological or psychiatric disorders Severe chronic metabolic diseases

Sponsors & Collaborators

• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: lead
• Università di Torino, Torino: collaborator
• Ospedale San Luigi Gonzaga, Orbassano: collaborator

Study Sites (2)

Università di Torino AOU San Luigi Gonzaga

Torino, to, 10043, Italy

WITHDRAWN

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma and DNA

MeSH Terms

Conditions

Dementia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Paola Caroppo, MD

CONTACT

02.2394.2260; paola.caroppo@istituto-besta.it

Aurora Romeo, SC

CONTACT

02.2394.2260; aurora.romeo@istituto-besta.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2025
• First Posted: October 6, 2025
• Study Start: June 5, 2023
• Primary Completion (Estimated): April 29, 2027
• Study Completion (Estimated): April 29, 2027
• Last Updated: February 11, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)