Acute Hydrocephaly, Brain Trauma, Neurological Disease Without Cognitive Degradation, Parkinson Disease, Probable Alzheimer Disease
Conditions
Keywords
Alzheimer disease (AD), diagnosis biomarkers, cerebrospinal fluid (CSF), targeted quantitative proteomics, mass spectrometry, stable isotope-labelled leucine
Brief 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.
Interventions
BIOLOGICALadministration 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
OTHERcollection 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
Assistance Publique - Hôpitaux de Paris
University Hospital, Clermont-Ferrand
International Atomic Energy Agency
University Hospital, Montpellier
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Reports written consent, informed and signed by the patient and a trusted person * Subject member or beneficiary of a social security system Specific criteria for group 1 and 2B : * Age between 55 and 85 years old for patients * Subject with AD or other neurodegenerative disease (frontotemporal dementia, dementia with Lewy bodies, Parkinson disease) * Subjects with chronic adult hydrocephalus (HCA) requiring depletion lumbar puncture (PL) Specific criteria for group 2A : \- Adult patient requiring neurosurgery with CSF shunt (subject with brain trauma, acute hydrocephaly) and favorable evolution that allows removal of the shunt
Exclusion criteria
* Patient deprived of liberty by judicial or administrative decision * Major protected by law * Pregnancy, women of childbearing age with risk of pregnancy, or breast-feeding * Presence of a transmissible viral disease (HlV, hepatitis B and C) * Patient included in a clinical trial * lnadequate cardiac, hepatic or severe renal disfunction * Disease amino acid metabolism (Leucinose..)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C13 Leucine incorporation in Amyloid peptides (1-40, 1-42) at different time points (in %) | 1.5 years | Analysis of labelled samples with mass spectrometry. Data generated will be studied to validate the experimental model and understand the pathophysiology of neurological disorders. A collection of labelled biological samples will also be generated. |
| C13 Leucine incorporation in detectable peptides generated after trypsin digestion of biological fluids from patients (CSF, blood, urine, saliva) (in %) | 1.5 years | C13 Leucine incorporation in detectable peptides generated after trypsin digestion of biological fluids from patients (CSF, blood, urine, saliva) (in %) |
Countries
France
Outcome results
None listed