ALZEVIT: Nationwide Digital APOE ε4 Cohort for Early Alzheimer's Disease Prevention and Trial Readiness

NCT07679906 | Recruiting DMC

• 2 other identifiers: ST0577ID RCB
• Study Type: observational
• Target: 50,000
• Locations: 1 country
• Sites: 1

Brief Summary

ALZEVIT is a nationwide, decentralized, digital-first cohort study in France designed to establish a large-scale Apolipoprotein E (APOE) genotyping registry and enable precision prevention strategies for Alzheimer's disease (AD). Sponsored by Firalis SA and conducted in collaboration with French memory centers, it addresses the need for early identification of individuals at high genetic risk, particularly APOE ε4 carriers and ε4/ε4 homozygotes, in the context of emerging disease-modifying therapies most effective in preclinical or early disease stages. Using an online recruitment platform, participants aged ≥45 years provide electronic informed consent and self-collected saliva samples via home collection kits for centralized APOE genotyping using the APO-Easy® assay, compliant with EU IVDR and US FDA requirements. Data are stored in a secure registry compliant with GDPR. Phase A (0-18 months) will enroll 50,000 participants to determine national APOE genotype distribution, identify high-risk individuals, and evaluate feasibility of large-scale digital genetic screening, with longitudinal online follow-up including cognitive and risk factor assessments. Phase B (12-24 months) includes detailed phenotyping of \~2,350 selected participants across all APOE genotypes, including \~750 ε4/ε4 homozygotes. Participants undergo clinical evaluation, MRI, cognitive testing, and multi-omics biomarker profiling (genomics, proteomics, metabolomics, environmental exposure), conducted at memory centers or via telemedicine. The study classifies participants along the cognitive continuum, including cognitively normal individuals, preclinical AD, mild cognitive impairment (MCI), and mild or moderate AD, to identify genotype-specific trajectories and modifiable risk and resilience factors. ALZEVIT aims to establish a scalable national infrastructure linking genetic stratification with longitudinal biomarker and clinical data to support prevention trials, improve understanding of APOE-related heterogeneity, and advance precision medicine for Alzheimer's disease.

Conditions

Alzheimer

Keywords

APOE ε4/ε4; Genetic Risk Profiling; Alzheimer's Disease

Outcome Measures

Primary Outcomes (4)

• 1. APOE genotype distribution in the study population

  Proportion and frequency of APOE genotypes (ε2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, ε4/ε4) in adults aged ≥45 years in France, stratified by age group.

  through study completion, an average of 2 years

• 2. Feasibility of large-scale decentralized APOE genotyping registry

  Operational performance of the digital-first model, including rates of electronic consent completion, home saliva kit return, DNA sample adequacy, and successful centralized APOE genoty

  through study completion, an average of 2 years

• 3. Identification of APOE ε4/ε4 homozygotes in the national cohort

  Number and proportion of ε4/ε4 individuals identified across age strata and successfully enrolled in the registry.

  through study completion, an average of 2 years

• 4. Establishment of a secure longitudinal APOE registry

  Creation of a GDPR-compliant database enabling longitudinal follow-up of participants with APOE genotype linked to minimal clinical and demographic data for future risk stratification and trial read

  through study completion, an average of 2 years

Study Arms (30)

ε2/ε2 (45-54)

ε2/ε2 (45-54)

ε2/ε2 (55-64)

ε2/ε2 (55-64)

ε2/ε2 (65-74)

ε2/ε2 (65-74)

ε2/ε2 (75-84)

ε2/ε2 (75-84)

ε2/ε2 (≥85)

ε2/ε2 (≥85)

ε2/ε3 (45-54)

ε2/ε3 (45-54)

ε2/ε3 (55-64)

ε2/ε3 (55-64)

ε2/ε3 (65-74)

ε2/ε3 (65-74)

ε2/ε3 (75-84)

ε2/ε3 (75-84)

ε2/ε3 (≥85)

ε2/ε3 (≥85)

ε2/ε4 (45-54)

ε2/ε4 (45-54)

ε2/ε4 (55-64)

ε2/ε4 (55-64)

ε2/ε4 (65-74)

ε2/ε4 (65-74)

ε2/ε4 (75-84)

ε2/ε4 (75-84)

ε2/ε4 (≥85)

ε2/ε4 (≥85)

ε3/ε4 (45-54)

ε3/ε4 (45-54)

ε3/ε4 (55-64)

ε3/ε4 (55-64)

ε3/ε4 (65-74)

ε3/ε4 (65-74)

ε3/ε4 (75-84)

ε3/ε4 (75-84)

ε3/ε4 (≥85)

ε3/ε4 (≥85)

ε3/ε3 (45-54)

ε3/ε3 (45-54)

ε3/ε3 (55-64)

ε3/ε3 (55-64)

ε3/ε3 (65-74)

ε3/ε3 (65-74)

ε3/ε3 (75-84)

ε3/ε3 (75-84)

ε3/ε3 (≥85)

ε3/ε3 (≥85)

ε4/ε4 (45-54)

ε4/ε4 (45-54)

ε4/ε4 (55-64)

ε4/ε4 (55-64)

ε4/ε4 (65-74)

ε4/ε4 (65-74)

ε4/ε4 (75-84)

ε4/ε4 (75-84)

ε4/ε4 (≥85)

ε4/ε4 (≥85)

Eligibility Criteria

• Age: 45 Years+
• Gender Eligibility Details: Male and Female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Phase A: ALZEVIT will enroll 50,000 French adults aged ≥45 years, stratified across five age groups. Participants will complete online risk-factor and cognitive assessments and provide a home-collected saliva sample for APOE genotyping. The study is expected to identify approximately 750 APOE ε4/ε4 homozygotes and establish a secure, GDPR-compliant national APOE registry. Phase B: A subset of 2,350 participants representing all six APOE genotypes, including 750 ε4/ε4 homozygotes, will undergo detailed clinical, cognitive, MRI, and biomarker evaluations. The objective is to characterize genotype-specific trajectories and classify participants according to Alzheimer's disease stage, from cognitively normal to preclinical AD, MCI-AD, and mild/moderate AD.

You may qualify if:

• Participants who sign the electronic Informed Consent form.
• Adults aged over 45 years old (inclusive) at the time of consent.
• Participants residing in France.
• Participants able to read and understand the study information in French or with the help of a legal representative.
• Participants are capable of electronically signing the consent form.
• Participants affiliated with the French national health insurance system.
• Participants with access to the internet and a valid email address.
• Participants can self-collect and return a saliva sample using a provided kit (ORAcollect® Dx device).

You may not qualify if:

• Participants who do not sign the Informed Consent form.
• Participants who are unable to read or understand French.
• Participants younger than 45 years at the time of consent.
• Participants with known cognitive impairments, severe dementia, or psychiatric conditions that prevent informed consent.
• Participants with a documented substance use disorder (alcohol or drug dependence) within the past 24 months.
• Participants who cannot be reliably contacted by email or phone.
• Participants previously enrolled in the ALZEVIT study or its pilot phase.
• Participants who are legally protected adults or under guardianship, curatorship, or judicial/administrative custody.
• Participants whose physical condition does not allow them to perform the tasks required by the study.
• Participants who, in the judgment of the Investigator, are unlikely to comply with study procedures.
• Participants who are study staff (investigators, sub-investigators, coordinators, assistants) or their immediate family members.
• Participants who are incarcerated or deprived of liberty by judicial or administrative decision.
• Participants with any disease or condition that, in the opinion of the Investigator, would compromise participation or safety.

Sponsors & Collaborators

• Firalis SA: lead
• CHU de Reims: collaborator
• University Hospital, Marseille: collaborator
• Centre Hospitalier Universitaire de Nice: collaborator
• University Hospital, Toulouse: collaborator
• Centre Hospitalier Universitaire de Besancon: collaborator
• University Hospital, Strasbourg, France: collaborator
• Centre Hospitalier de Colmar: collaborator
• University Hospital, Montpellier: collaborator

Study Sites (1)

FIRALIS SA - Centre de Prélèvements Biologiques

Huningue, 68330, France

RECRUITING

Related Publications (2)

• Williams DM, Heikkinen S, Hiltunen M; FinnGen; Davies NM, Anderson EL. The proportion of Alzheimer's disease attributable to apolipoprotein E. NPJ Dement. 2026;2(1):1. doi: 10.1038/s44400-025-00045-9. Epub 2026 Jan 9.

  PMID: 41522467 BACKGROUND

• APOE4 Homozygotes Represent a Distinct Genetic Subtype of Alzheimer's Disease. Am J Med Genet A. 2024 Aug;194(8):e63280. doi: 10.1002/ajmg.a.63280. No abstract available.

  PMID: 38962898 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Saliva samples (home-collected in Phase A for APOE genotyping), whole blood samples (Phase B clinical collection for genetic and biomarker analyses), plasma samples (derived from blood for circulating biomarker assessment), serum samples (for biochemical and protein biomarker studies), and urine samples (for metabolomic and environmental exposure analyses).

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Audrey GABELLE,, MD, PhD

  CMRR Languedoc-Roussillon - Montpellier

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hüseyin FIRAT, MD, PhD, HDR

CONTACT

+33 (0) 389 911 321; hueseyin.firat@firalis.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: July 1, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)