New Biomarker for Alzheimer's Disease Diagnostic

Alzheimer's Disease, Mild Cognitive Impairment

Dementia, Cognitive impairment, Memory impairment, Mild Cognitive Impairment, Cerebrospinal fluid, Plasma, Biomarker, Longitudinal, Abeta peptide amyloid, saPP alpha, Oculomotor impairment

The aim of this study is to examine the relationship between plasma putative biomarkers for Alzheimer's disease (i.e. Ab40 amyloid and total Ab42 amyloid, free, bound, free/bound, truncated, sAPPα) and : * the risk of conversion of individuals with Mild Cognitive Impairment (MCI) into Alzheimer's disease (AD), * the Alzheimer's disease progression rate.

Rational Whether there are biological markers of Alzheimer's disease (AD) is crucial for adequate targeting and appropriate management of the disease. The aim of our study is to examine diagnostic performance and predictive and prognostic values of new plasma markers of AD. Results of studies on the predictive value of plasma concentrations of Aβ40 and 42 amyloid peptides for incident AD are not straightforward. Discrepancies in these results may be due to the fact that total peptide concentrations have been measured. One recent study suggests that plasma free Aβ peptide concentration and particularly low-density lipoprotein receptor-related protein (LPR) as like as free Aβ/total Aβ ratio would be more reliable and discriminant. Main objective of the study To examine the association between plasma free Aβ peptide concentration and (1) the risk of conversion of subjects with Mild Cognitive Impairment (MCI) into Alzheimer's disease (AD) and (2) the risk of worsening of the disease in patients with mild and moderate stages of AD. Secondary objectives * To examine the association of total peptid Aβ concentration, free Aβ/Total Aβ ratio, and trunked plasmatic Aβ to the risk of incident AD in MCI subjects, and to the risk of worsening of the disease in mild and moderate AD patients, * To examine the association between serum sAPP concentration and the risk of incident AD in MCI subjects, and the risk of worsening of the disease in mild and moderate AD patients, * To compare the time evolution of concentrations of these biomarkers to Alzheimer's disease progression rate which will be assessed on the basis of neuropsychological examinations and MRI examination of hippocampal atrophy, * To examine the association between serum and cerebrospinal fluid (CSF) concentrations of AD biomarkers in subgroup of participants who undergo lumbar puncture, * To examine the association between neuroimaging data (cerebral volume, hippocampal volume, cerebrovascular lesions and plasma and CSF AD biomarkers' concentrations, * To constitute blood and plasma banks, gene bank and CSF bank for future studies on other biomarkers of AD. Design and Methods Longitudinal multicenter study including 1300 subjects with amnestic impairment (MCI, n=650 and AD, n=650) derived from the main French national Memory Resources and Research Centers. Participants will undergo at baseline and every 6 months a neurological examination, a neuropsychological assessment (and an oculomotor examination for those included from Broca Hospital). Alzheimer disease biomarkers' measurements will be performed at inclusion and at the end of the study. For those MCI participants who convert to dementia, the end of the study will correspond to the AD conversion period. A Magnetic Resonance Imaging (MRI) scan will be performed at inclusion and at the end of the study for MCI subjects who convert into AD. A lumbar puncture on an outpatient basis will be performed at study entry in all participants who will give an informed consent for this examination in absence of contraindication.

France