Mitochondrial Function and Metabolomic Profile in Alzheimer's Disease and Related Dementias

Centre Hospitalier Universitaire de Nice170 enrolled

Overview

This project aims to study on one hand the early mitochondrial alterations, common or specific, occurring in peripheral cells of patients with Alzheimer's disease or related dementia and, on the other hand, identify the metabolomic biomarkers that may be at the origin of mitochondrial disturbances associated with the disease. This will be the first study combining functional analyses of mitochondria and exploratory metabolomic assessments in the same cohort at early stages of the disease.

Study will be proposed to the patient of the Nice Memory center who had a lumbar puncture and who agreed on the storage of a sample of their cerebrospinal fluid. Two groups of patients will be compared: the Alzheimer"s disease patient with positive amyloid on the cerebrospinal fluid and the non Alzheimer patient with negative amyloid on the cerebrospinal fluid. Blood samples will be collected at inclusion and one year to obtain the mitochondrial metabolomic signature

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

170

Conditions

Alzheimer Disease

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Neurocognitive disorder with spontaneous complaint or reported for at least 6 months * Diagnostic process according to current Haute Autorité de Santé (HAS) recommendations. * cerebrospinal fluid biomarker dosage done within the study center and agreement to bio-collection of residual cerebrospinal fluid * Patient having agreed to sign the informed consent * Patient affiliated or beneficiary of a social security scheme For alzheimer group : diagnosis of Alzheimer's disease according to NIA-AA 2024 criteria (presence of a pathogenic amyloid process in the cerebrospinal fluid) For non alzheimer group : diagnosis of mild or major neurocognitive disorder according to Manuel diagnostique et statistique des troubles mentaux edition 5 (DSM-V) criteria, not linked to Alzheimer's disease (absence of pathogenic amyloid process in the cerebrospinal fluid) Exclusion Criteria: \- Vulnerable people

Outcomes

Primary Outcomes

Mitochondrial oxygen consumption of peripheral blood cells

Comparison of the rate of mitochondrial oxygen consumption of peripheral blood cells between alzheimer (amyloid positive) and non-Alzheimer participant (amyloid negative) in pmol/min/cell mesured by Extracellular Flux Analyzer

Time frame: At Baseline

Mitochondrial oxygen consumption of peripheral blood cells

Time frame: At 1 year

Secondary Outcomes

Mitochondrial metabolomic signature

Description of the panel of mitochondrial metabolites of peripheral blood cells according to the status of the participants (amyloid positive vs amyloid negative).

Time frame: At Baseline and at one year

Mini Mental State Examination Scores for Cognitive Impairment

30 questions, good response to a question = 1, bad response to a question = 0, global scoring between 0 and 30, Pathological threshold according to the socio-cultural level : without diploma : total score \<22 secondary education without the 3rd class : total score \<23 secondary education from 3rd class to the senior year class (without bachelor degree) higher education : total score \<26