CLarifying ABCB1's Role in Alzheimer's Disease (CLeAR-AD)

CLarifying ABCB1's Role in Amyloid Efflux and Alzheimer's Disease Risk

Alzheimer's disease is biologically defined by the accumulation of amyloid beta and tau protein, identified using cerebrospinal fluid biomarkers. The ABCB1 gene, which encodes P-glycoprotein involved in amyloid beta efflux across the blood-brain barrier, may influence Alzheimer's disease risk. We hypothesize that certain functional ABCB1 polymorphisms impair amyloid beta clearance, thereby promoting the development of biologically defined Alzheimer's disease.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Genetic: ABCB1 genotyping

Detailed Description

A case-control study comparing the distribution of three functional ABCB1 gene polymorphisms (3435C>T, 2677G>T/A, 1236C>T) in patients with biologically defined Alzheimer's disease versus neurological controls. We will also analyze the distribution of haplotypes derived from the combination of these three polymorphisms and investigate potential interactions between these polymorphisms and the APOE genotype, particularly the presence of the ε4 allele.

• Study Type: Observational
• Enrollment (Actual): 510

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Hôpital Lariboisière - Fernand Widal (AP - HP)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients followed in a memory clinic who underwent a comprehensive clinical and paraclinical assessment, including cerebrospinal fluid biomarkers.

Description

Inclusion Criteria:

• age ≥ 50 years,
• available cerebrospinal fluid biomarker results,
• an available and usable DNA sample,
• and consent for future research use within the biobank.

Exclusion Criteria:

• the presence of an active non-degenerative neurological disorder (for example, multiple sclerosis, infections, or tumors),
• and missing data regarding APOE genotyping or cardiovascular risk factors

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with cerebrospinal fluid amyloid and phosphorylated tau biomarkers (A+T+)	Genetic: ABCB1 genotyping; Genotyping of three single nucleotide polymorphisms (3435C>T, 2677G>T/A, and 1236C>T) associated with variation in P-glycoprotein activity, using DNA samples stored in a biobank.
Patients without cerebrospinal fluid amyloid, phosphorylated tau and total tau biomarkers (A-T-N-)	Genetic: ABCB1 genotyping; Genotyping of three single nucleotide polymorphisms (3435C>T, 2677G>T/A, and 1236C>T) associated with variation in P-glycoprotein activity, using DNA samples stored in a biobank.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Allele and genotype frequencies of ABCB1 single nucleotide polymorphisms (3435C>T, 2677G>T/A, and 1236C>T)	Allele and genotype frequencies of the ABCB1 single nucleotide polymorphisms 3435C>T, 2677G>T/A, and 1236C>T, determined by genotyping from genomic DNA, will be compared between: patients with biologically defined Alzheimer's disease (A+T+Nx), and; neurological control participants with a negative biomarker profile (A-T-N-). Data will be summarized as allele frequencies and genotype distributions in each group.	Baseline (at the time of biological sampling and clinical assessment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haplotype frequencies of ABCB1 polymorphisms (3435C>T, 2677G>T/A, and 1236C>T)	Haplotype frequencies derived from the combination of the ABCB1 single nucleotide polymorphisms 3435C>T, 2677G>T/A, and 1236C>T, inferred from genotyping data, will be compared between: patients with biologically defined Alzheimer's disease (A+T+Nx), and; neurological control participants with a negative biomarker profile (A-T-N-). Haplotypes will be summarized as frequency distributions within each group.	Baseline (at the time of biological sampling and clinical assessment)
Distribution of ABCB1 polymorphisms stratified by APOE ε4 carrier status	The distribution of ABCB1 single nucleotide polymorphisms (3435C>T, 2677G>T/A, and 1236C>T) will be assessed according to APOE ε4 carrier status (ε4 carriers vs non-carriers) in: patients with biologically defined Alzheimer's disease (A+T+Nx), and; neurological control participants with a negative biomarker profile (A-T-N-). ABCB1 allele and genotype frequencies will be summarized within each APOE ε4 stratum.	Baseline (at the time of biological sampling and clinical assessment)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2023
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: January 19, 2026
• First Submitted That Met QC Criteria: January 30, 2026
• First Posted (Actual): February 6, 2026

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: January 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer Disease; P-glycoprotein
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: APHP251732

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No