Validation of Blood Biomarkers for Alzheimer's Disease

Rationale of the project:

Recent progress in the biological diagnosis of Alzheimer's disease (AD) is considerable, with the possibility, thanks in particular to ultra-sensitive tests, of having relevant blood biomarkers. These biomarkers, mainly represented by amyloid peptides, tau proteins and neurofilaments, make it possible to consider a stratification of patients according to different classifications, including the ATN scale. Their diagnostic value has been mainly tested on retrospective samples and it is now essential to use them prospectively to confront them with pre-analytical and analytical variability. It is also important to position them in relation to CSF analysis and AD management, from risk assessment, diagnosis, to therapeutic strategies.

Main objective:

To evaluate, in a prospective consecutive enrollment clinical trial, the diagnostic performance (sensitivity, specificity) of blood biomarkers for Alzheimer's disease.

Secondary objectives:

• Interest of blood biomarkers for detection of normal/pathological CSF profiles.
• Interest of blood biomarkers for other disease including, amyloid angiopathy, frontotemporal dementia (FTD) or lewy body disease (LBD).

Methodology:

The investigator's laboratory daily receives CSF samples from regional "memory clinics" (mainly from Montpellier, Nîmes, Perpignan) for Aß40, Aß42, t-Tau and p-Tau(181) assays. The results of these tests performed weekly on an automated platform are used by neurologists for the diagnosis of AD. In this non-interventional multi-center clinical trial, with the informed consent of patients, one tube of plasma in addition to CSF is collected. In parallel with the CSF, amyloid peptides and plasma p-Tau is measured. The ApoE4 status will also be determined using MS as previously published by the investigator's group. Plasma biomarkers will then be combined to confirm the presence of AD, as has already been done on retrospective samples by the investigator's laboratory and others. Considering a disease prevalence rate of 20% in the screened population, and to reach a sensitivity of 80% and a specificity close to 90%, it is necessary to include a total of 311 patients in order to obtain an estimate of sensitivity and specificity with a 95% accuracy of +/- 10%. The lost to follow-up rate of about 10% requires the enrollment of 342 patients. The diagnostic performance of this profile will be compared to that of CSF, as well as to the diagnosis assessed by a multidisciplinary team one year after sampling.

Expected benefit:

The confirmation that blood biomarkers of AD achieve satisfactory diagnostic performance in a clinical setting allows them to be considered in routine use, as a less invasive method, thus with greater acceptance and also the possibility of longitudinal use. The benefit also lies in the evaluation of the interest of supplemental biomarkers such as NfL, for related diseases.

Inclusion criteria

• Patients consulting in memory clinics from Montpellier, Nîmes, or Perpignan.
• Age >= 18 years old
• CSF AD biomarkers performed for diagnostic purpose in clinical routine practice
• Having given their written and enlightened consent
• Affiliated or beneficiary of the national health insurance

Exclusion criteria

• Contraindication or refusal of lumbar puncture
• Patient deprived of freedom, by court or administrative order, or major protected by law
• Pregnant or breastfeeding women