Alzheimer Disease
Conditions
Keywords
Alzheimer Disease, P-glycoprotein
Brief summary
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.
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.
Interventions
GENETICABCB1 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.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Allele and genotype frequencies of ABCB1 single nucleotide polymorphisms (3435C>T, 2677G>T/A, and 1236C>T) | Baseline (at the time of biological sampling and clinical assessment) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Haplotype frequencies of ABCB1 polymorphisms (3435C>T, 2677G>T/A, and 1236C>T) | Baseline (at the time of biological sampling and clinical assessment) | 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. |
| Distribution of ABCB1 polymorphisms stratified by APOE ε4 carrier status | Baseline (at the time of biological sampling and clinical assessment) | 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. |
Countries
France
Outcome results
None listed