In Vivo Alzheimer Proteomics

Summary

In France, an estimated 860 000 patients are affected by Alzheimer Disease (AD) which represents, as in other developed countries, a major public health issue. In many cases, AD diagnosis is uncertain and its clinical evolution unpredictable. The exactitude of the diagnosis is however particularly important in the perspective of the validation and use of new therapeutic strategies in AD. Detection of cerebrospinal fluid (CSF) diagnosis biomarkers fell short in the detection, of atypical/mixed cases, of some differential diagnosis, and in differentiating rapid or slow clinical evolutions. Hence, CSF analysis gives a unique opportunity to detect and validate biomarkers in many neurological disorders. Nevertheless, in medical practice, CSF biological analysis is currently limited to a small number of analytes.Quantitative and targeted mass spectrometry, especially operated in the Multiple reaction monitoring mode (MRM), represents an alternative to immunodetection and could be used to detect specific biomarkers in complex matrices such as plasma by specifically discriminating the proteotypic peptides corresponding to each proteins. Mass spectrometry has also the ability to distinguish and quantify isotopically labelled and unlabeled selected targets. This ability was used in a publication by the group of R. Bateman (Washington University, St Louis, USA) who could, after administering stable isotope-labelled leucine, evaluate Ab synthesis and clearance in humans. This approach has an enormous potential to study the metabolism of proteins within the human CNS and consequently help in the understanding and diagnosis of neurological disorders.The main objective of this program is set up a targeted quantitative mass spectrometry method for existing and stable isotope-labelled CSF biomarkers in the neurological field; exploit this approach for diagnostic purpurses and to gain knowledge in the pathophysiology of diseases.

Conditions

• Probable Alzheimer Disease
• Parkinson Disease
• Neurological Disease Without Cognitive Degradation
• Brain Trauma
• Acute Hydrocephaly

Interventions

BIOLOGICAL

administration of stable isotope-labelled leucine-

\- administration of stable isotope-labelled leucine : by drip, for group 2A and group 2B. Group 1 (control group) : 1 collection of CSF. Group 2B : 4 collections of CSF, 24 hours after administration of stable isotope-labelled leucin. Group 2A (patients with brain trauma, acute hydrocephaly) : continuous collection of CSF, for 24 to 36 hours

OTHER

collection of CSF, blood, urine, saliva

\- administration of stable isotope-labelled leucine : by drip, for group 2A and group 2B. Group 1 (control group) : 1 collection of CSF. Group 2B : 4 collections of CSF, 24 hours after administration of stable isotope-labelled leucin. Group 2A (patients with brain trauma, acute hydrocephaly) : continuous collection of CSF, for 24 to 36 hours

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris

  collaborator OTHER

• University Hospital, Clermont-Ferrand

  collaborator OTHER

• International Atomic Energy Agency

  collaborator OTHER_GOV

• University Hospital, Montpellier

  lead OTHER

Principal Investigators

• Sylvain Lehmann, PU-PH · Laboratoire de Biochimie et Protéomique Clinique, IRMB St Eloi, CHRU de Montpellier

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

55 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-10-08

Primary Completion

2018-05-22

Completion

2018-05-22

Countries

• France

Study Locations