Audrey Gabelle - Academia.edu (original) (raw)
Papers by Audrey Gabelle
Alzheimer's Research & Therapy, 2015
Bookmarks Related papers MentionsView impact
![Research paper thumbnail of [Injectable preparation of labeled leucine with the carbon 13 for a clinical research program on the Alzheimer disease: pharmaceutical control of raw materials and the finished product and stability study]](https://attachments.academia-assets.com/42543368/thumbnails/1.jpg)
](Annales pharmaceutiques françaises, 2015
The L-leucine labeled (L-[U-(13)C] Leu) is a stable isotopic tracer administered by parenteral ro... more The L-leucine labeled (L-[U-(13)C] Leu) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the diagnosis of the Alzheimer's disease. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of raw materials and the finished product followed by a stability study were realised. After the pharmaceutical control of raw materials, the solution of L-[U-(13)C] Leu was prepared according to the good practices preparation. Prepared bottles were stored for 1 year of a share in a climatic chamber (25 °C±2 °C) and the other in a refrigerator (5 °C±3 °C). To assess stability, the physicochemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C] Leu concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility) were performed at regular intervals for 1 year. Neither significant decrease of L-[U-(13)C]...
Bookmarks Related papers MentionsView impact
Alzheimer's & dementia : the journal of the Alzheimer's Association, Jan 15, 2014
Bookmarks Related papers MentionsView impact
Frontiers in aging neuroscience, 2014
To examine relationships between cerebrospinal fluid (CSF) Alzheimer' disease (AD) biomarkers... more To examine relationships between cerebrospinal fluid (CSF) Alzheimer' disease (AD) biomarkers and hypocretin-1 levels in patients with cognitive abnormalities and hypocretin-deficient narcolepsy-cataplexy (NC), estimate diagnostic accuracy, and determine correlations with sleep disturbances. Sleep disturbances are frequent in AD. Interactions between brain β-amyloid (Aβ) aggregation and a wake-related neurotransmitter hypocretin have been reported in a mouse model of AD. Ninety-one cognitive patients (37 AD, 16 mild cognitive impairment-MCI that converts to AD, 38 other dementias) and 15 elderly patients with NC were recruited. Patients were diagnosed blind to CSF results. CSF Aβ42, total tau, ptau181, and hypocretin-1 were measured. Sleep disturbances were assessed with questionnaires in 32 cognitive patients. Lower CSF Aβ42 but higher tau and P-tau levels were found in AD and MCI compared to other dementias. CSF hypocretin-1 levels were higher in patients with MCI due to AD co...
Bookmarks Related papers MentionsView impact
Journal of Alzheimer's disease : JAD, 2014
Alzheimer's disease (AD) clinical onset is usually characterized by a memory complaint and a ... more Alzheimer's disease (AD) clinical onset is usually characterized by a memory complaint and a progressive memory deficit. The proportion of typical medial-temporal amnesia revealing AD remains unknown. The present study explores the episodic memory impairment profiles by the Free and Cued Selective Recall Reminding Test (FCSRT) in patients with initial memory complaint and a cerebrospinal fluid (CSF) biomarker signature of AD. Seventy-three patients referred for memory complaint to the Centers for Memory, Resource and Research of Lyon and Montpellier (France) were included consecutively. All patients underwent an extensive neuropsychological examination and had a Mini-Mental State Examination (MMSE) score ≥20 and a positive CSF AD signature. The patients were classified as having mild dementia or prodromal AD. Verbal episodic memory was assessed using the French version of the FCSRT exploring encoding, storage/consolidation, and cued delayed retrieval phases of memorization. Thre...
Bookmarks Related papers MentionsView impact
The Journal of Nutrition Health and Aging, 2008
Background : Alzheimer's disease (AD) is a devas... more Background : Alzheimer's disease (AD) is a devastating neurodegenerative affection that is approaching epidemic proportions in the industrialized world due to aging of the populations. Recently, new revisited AD diagnosis criteria point out the major interest of CSF biomarkers. The dosage ...
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Background : Alzheimer’s disease (AD) is a devastating neurodegenerative affection that is approa... more Background : Alzheimer’s disease (AD) is a devastating neurodegenerative affection that is approaching epidemic proportions in the industrialized world due to aging of the populations. Recently, new revisited AD diagnosis criteria point out the major interest of CSF biomarkers. The dosage of tau, its phosphorylated form p-tau181 and amyloïd Aβ42 peptide in CSF have come to the fore. Based on Aβ42 and tau values obtained using Innogenetics ELSIA kits, a index called IATI could be calculated and seemed very interesting to discriminate AD from other dementias. Aim : To investigate the diagnostic value of CSF IATI in AD positive diagnosis. Method : CSF tau, p-tau181 and Aβ42 biomarkers were analysed in a consecutive cohort of 167 patients with neurological disease. Eighteen AD and 46 non Alzheimer’s dementias were identified in this population. The AD diagnosis was based on NINCDS/ADRDA criteria. Lombar punctures were performed after informed consent was obtained from the patient or the...
Bookmarks Related papers MentionsView impact
The journal of nutrition, health & aging, 2010
Bookmarks Related papers MentionsView impact
Alzheimer's & Dementia, 2014
Bookmarks Related papers MentionsView impact
Alzheimer's Research & Therapy, 2014
The relevance of the cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer&... more The relevance of the cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer's disease (AD) and related disorders is clearly established. However, the question remains on how to use these data, which are often heterogeneous (not all biomarkers being pathologic). The objective of this study is to propose to physicians in memory clinics a biologic scale of probabilities that the patient with cognitive impairments has an Alzheimer's disease (AD) pathologic process. For that purpose, we took advantage of the multicenter data of our Paris-North, Lille, and Montpellier (PLM) study, which has emerged through the initial sharing of information from these memory centers. Different models combining the CSF levels of amyloid-β 42, tau, and p-tau(181) were tested to generate categories of patients with very low (<10%), low (<25%), high (>75%), and very high predictive values (>90%) for positive AD. In total, 1,273 patients (646 AD and 627 non-AD) from six independent memory-clinic cohorts were included. A prediction model based on logistic regressions achieved a very good stratification of the population but had the disadvantages of needing mathematical optimization and being difficult to use in daily clinical practice. Remarkably, a simple and intuitive model based on the number (from zero to three) of three pathologic CSF biomarkers resulted in a very efficient predictive scale for AD in patients seen in memory clinics. The scale's overall predictive value for AD for the different categories were as follows: class 0, 9.6% (95% confidence interval (CI), 6.0% to 13.2%); class 1, 24.7% (95% CI, 18.0% to 31.3%); class 2, 77.2% (95% CI, 67.8% to 86.5%); and class 3, 94.2% (95% CI, 90.7% to 97.7%). In addition, with this scale, significantly more patients were correctly classified than with the logistic regression. Its superiority in model performance was validated by the computation of the net reclassification index (NRI). The model was also validated in an independent…
Bookmarks Related papers MentionsView impact
Revue Neurologique, 2009
Bookmarks Related papers MentionsView impact
Revue Neurologique, 2010
Bookmarks Related papers MentionsView impact
PROTEOMICS – CLINICAL APPLICATIONS, 2008
Bookmarks Related papers MentionsView impact
PLoS ONE, 2014
Bookmarks Related papers MentionsView impact
Journal of Neurology, 2012
Bookmarks Related papers MentionsView impact
Journal of Immunological Methods, 2008
Bookmarks Related papers MentionsView impact
Journal of Clinical Neurophysiology, 2011
This study was designed to evaluate the predictive value of event-related potential (ERP; N2 and ... more This study was designed to evaluate the predictive value of event-related potential (ERP; N2 and P3b) in patients with mild cognitive impairment (MCI). Seventy-one patients with MCI were selected and compared with 31 healthy control subjects. They benefited from an initial assessment that included a neuropsychological evaluation and ERP. We followed them up for 1 year, and during their last visit, they benefited again from ERP and neuropsychological tests. At the end of the study, 2 subgroups of patients with MCI were differentiated according to their clinical evolution from baseline to follow-up: 41 MCI progressors (MCI-P) and 30 MCI nonprogressors (MCI-non P). The MCI-P patients had a significant decline in their executive functions compared with the MCI-non-P group at baseline and follow-up especially on trail making test B (TMT B) and verbal fluency (P < 0.0001). At baseline, MCI-P had increased P3b latencies and low P3b amplitudes compared with MCI-non P. The MCI-P showed an inversion of the P3b rostrocaudal gradient with a significant decrease in the amplitude of P3b in the parietal area compared with the MCI-non P. At follow-up, 17 MCI-P patients had converted to Alzheimer's disease (AD). There was a significant rate of decline of the amplitude of N2 and P3b in the frontal area among the groups. Furthermore, the MCI-P had a higher decrease in the rostrocaudal gradient of P3b and prolonged N2 and P3b latencies than the MCI-non P did. The sensitivity and specificity were approximately 80% and 70%, using P3b amplitude to discriminate the MCI-P from the MCI-non P. Our study underlines the interest of using N2 and P3b as neurophysiological markers for measuring MCI decline progression.
Bookmarks Related papers MentionsView impact
Brain, 2013
Bookmarks Related papers MentionsView impact
Brain Research, 2010
Bookmarks Related papers MentionsView impact
Alzheimer's Research & Therapy, 2015
Bookmarks Related papers MentionsView impact
Annales pharmaceutiques françaises, 2015
The L-leucine labeled (L-[U-(13)C] Leu) is a stable isotopic tracer administered by parenteral ro... more The L-leucine labeled (L-[U-(13)C] Leu) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the diagnosis of the Alzheimer's disease. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of raw materials and the finished product followed by a stability study were realised. After the pharmaceutical control of raw materials, the solution of L-[U-(13)C] Leu was prepared according to the good practices preparation. Prepared bottles were stored for 1 year of a share in a climatic chamber (25 °C±2 °C) and the other in a refrigerator (5 °C±3 °C). To assess stability, the physicochemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C] Leu concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility) were performed at regular intervals for 1 year. Neither significant decrease of L-[U-(13)C]...
Bookmarks Related papers MentionsView impact
Alzheimer's & dementia : the journal of the Alzheimer's Association, Jan 15, 2014
Bookmarks Related papers MentionsView impact
Frontiers in aging neuroscience, 2014
To examine relationships between cerebrospinal fluid (CSF) Alzheimer' disease (AD) biomarkers... more To examine relationships between cerebrospinal fluid (CSF) Alzheimer' disease (AD) biomarkers and hypocretin-1 levels in patients with cognitive abnormalities and hypocretin-deficient narcolepsy-cataplexy (NC), estimate diagnostic accuracy, and determine correlations with sleep disturbances. Sleep disturbances are frequent in AD. Interactions between brain β-amyloid (Aβ) aggregation and a wake-related neurotransmitter hypocretin have been reported in a mouse model of AD. Ninety-one cognitive patients (37 AD, 16 mild cognitive impairment-MCI that converts to AD, 38 other dementias) and 15 elderly patients with NC were recruited. Patients were diagnosed blind to CSF results. CSF Aβ42, total tau, ptau181, and hypocretin-1 were measured. Sleep disturbances were assessed with questionnaires in 32 cognitive patients. Lower CSF Aβ42 but higher tau and P-tau levels were found in AD and MCI compared to other dementias. CSF hypocretin-1 levels were higher in patients with MCI due to AD co...
Bookmarks Related papers MentionsView impact
Journal of Alzheimer's disease : JAD, 2014
Alzheimer's disease (AD) clinical onset is usually characterized by a memory complaint and a ... more Alzheimer's disease (AD) clinical onset is usually characterized by a memory complaint and a progressive memory deficit. The proportion of typical medial-temporal amnesia revealing AD remains unknown. The present study explores the episodic memory impairment profiles by the Free and Cued Selective Recall Reminding Test (FCSRT) in patients with initial memory complaint and a cerebrospinal fluid (CSF) biomarker signature of AD. Seventy-three patients referred for memory complaint to the Centers for Memory, Resource and Research of Lyon and Montpellier (France) were included consecutively. All patients underwent an extensive neuropsychological examination and had a Mini-Mental State Examination (MMSE) score ≥20 and a positive CSF AD signature. The patients were classified as having mild dementia or prodromal AD. Verbal episodic memory was assessed using the French version of the FCSRT exploring encoding, storage/consolidation, and cued delayed retrieval phases of memorization. Thre...
Bookmarks Related papers MentionsView impact
The Journal of Nutrition Health and Aging, 2008
Background : Alzheimer's disease (AD) is a devas... more Background : Alzheimer's disease (AD) is a devastating neurodegenerative affection that is approaching epidemic proportions in the industrialized world due to aging of the populations. Recently, new revisited AD diagnosis criteria point out the major interest of CSF biomarkers. The dosage ...
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Background : Alzheimer’s disease (AD) is a devastating neurodegenerative affection that is approa... more Background : Alzheimer’s disease (AD) is a devastating neurodegenerative affection that is approaching epidemic proportions in the industrialized world due to aging of the populations. Recently, new revisited AD diagnosis criteria point out the major interest of CSF biomarkers. The dosage of tau, its phosphorylated form p-tau181 and amyloïd Aβ42 peptide in CSF have come to the fore. Based on Aβ42 and tau values obtained using Innogenetics ELSIA kits, a index called IATI could be calculated and seemed very interesting to discriminate AD from other dementias. Aim : To investigate the diagnostic value of CSF IATI in AD positive diagnosis. Method : CSF tau, p-tau181 and Aβ42 biomarkers were analysed in a consecutive cohort of 167 patients with neurological disease. Eighteen AD and 46 non Alzheimer’s dementias were identified in this population. The AD diagnosis was based on NINCDS/ADRDA criteria. Lombar punctures were performed after informed consent was obtained from the patient or the...
Bookmarks Related papers MentionsView impact
The journal of nutrition, health & aging, 2010
Bookmarks Related papers MentionsView impact
Alzheimer's & Dementia, 2014
Bookmarks Related papers MentionsView impact
Alzheimer's Research & Therapy, 2014
The relevance of the cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer&... more The relevance of the cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer's disease (AD) and related disorders is clearly established. However, the question remains on how to use these data, which are often heterogeneous (not all biomarkers being pathologic). The objective of this study is to propose to physicians in memory clinics a biologic scale of probabilities that the patient with cognitive impairments has an Alzheimer's disease (AD) pathologic process. For that purpose, we took advantage of the multicenter data of our Paris-North, Lille, and Montpellier (PLM) study, which has emerged through the initial sharing of information from these memory centers. Different models combining the CSF levels of amyloid-β 42, tau, and p-tau(181) were tested to generate categories of patients with very low (<10%), low (<25%), high (>75%), and very high predictive values (>90%) for positive AD. In total, 1,273 patients (646 AD and 627 non-AD) from six independent memory-clinic cohorts were included. A prediction model based on logistic regressions achieved a very good stratification of the population but had the disadvantages of needing mathematical optimization and being difficult to use in daily clinical practice. Remarkably, a simple and intuitive model based on the number (from zero to three) of three pathologic CSF biomarkers resulted in a very efficient predictive scale for AD in patients seen in memory clinics. The scale's overall predictive value for AD for the different categories were as follows: class 0, 9.6% (95% confidence interval (CI), 6.0% to 13.2%); class 1, 24.7% (95% CI, 18.0% to 31.3%); class 2, 77.2% (95% CI, 67.8% to 86.5%); and class 3, 94.2% (95% CI, 90.7% to 97.7%). In addition, with this scale, significantly more patients were correctly classified than with the logistic regression. Its superiority in model performance was validated by the computation of the net reclassification index (NRI). The model was also validated in an independent…
Bookmarks Related papers MentionsView impact
Revue Neurologique, 2009
Bookmarks Related papers MentionsView impact
Revue Neurologique, 2010
Bookmarks Related papers MentionsView impact
PROTEOMICS – CLINICAL APPLICATIONS, 2008
Bookmarks Related papers MentionsView impact
PLoS ONE, 2014
Bookmarks Related papers MentionsView impact
Journal of Neurology, 2012
Bookmarks Related papers MentionsView impact
Journal of Immunological Methods, 2008
Bookmarks Related papers MentionsView impact
Journal of Clinical Neurophysiology, 2011
This study was designed to evaluate the predictive value of event-related potential (ERP; N2 and ... more This study was designed to evaluate the predictive value of event-related potential (ERP; N2 and P3b) in patients with mild cognitive impairment (MCI). Seventy-one patients with MCI were selected and compared with 31 healthy control subjects. They benefited from an initial assessment that included a neuropsychological evaluation and ERP. We followed them up for 1 year, and during their last visit, they benefited again from ERP and neuropsychological tests. At the end of the study, 2 subgroups of patients with MCI were differentiated according to their clinical evolution from baseline to follow-up: 41 MCI progressors (MCI-P) and 30 MCI nonprogressors (MCI-non P). The MCI-P patients had a significant decline in their executive functions compared with the MCI-non-P group at baseline and follow-up especially on trail making test B (TMT B) and verbal fluency (P < 0.0001). At baseline, MCI-P had increased P3b latencies and low P3b amplitudes compared with MCI-non P. The MCI-P showed an inversion of the P3b rostrocaudal gradient with a significant decrease in the amplitude of P3b in the parietal area compared with the MCI-non P. At follow-up, 17 MCI-P patients had converted to Alzheimer's disease (AD). There was a significant rate of decline of the amplitude of N2 and P3b in the frontal area among the groups. Furthermore, the MCI-P had a higher decrease in the rostrocaudal gradient of P3b and prolonged N2 and P3b latencies than the MCI-non P did. The sensitivity and specificity were approximately 80% and 70%, using P3b amplitude to discriminate the MCI-P from the MCI-non P. Our study underlines the interest of using N2 and P3b as neurophysiological markers for measuring MCI decline progression.
Bookmarks Related papers MentionsView impact
Brain, 2013
Bookmarks Related papers MentionsView impact
Brain Research, 2010
Bookmarks Related papers MentionsView impact