ORCID Profile
0000-0001-6117-562X
Current Organisations
Université de Strasbourg
,
Université de Strasbourg Faculté de Médecine
,
Centre Hospitalier Universitaire de Montpellier
,
Université de Montpellier
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Publications
A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease
Publisher: Springer Science and Business Media LLC
Date: 03-2020
Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome: a cross-sectional study
Publisher: Elsevier BV
Date: 06-2020
Operational definition of Active and Healthy Ageing (AHA): A conceptual framework
Publisher: Springer Science and Business Media LLC
Date: 19-09-2015
DOI: 10.1007/S12603-015-0589-6
Abstract: Health is a multi-dimensional concept, capturing how people feel and function. The broad concept of Active and Healthy Ageing was proposed by the World Health Organisation (WHO) as the process of optimizing opportunities for health to enhance quality of life as people age. It applies to both in iduals and population groups. A universal Active and Healthy Ageing definition is not available and it may differ depending on the purpose of the definition and/or the questions raised. While the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has had a major impact, a definition of Active and Healthy Ageing is urgently needed. A meeting was organised in Montpellier, France, October 20-21, 2014 as the annual conference of the EIP on AHA Reference Site MACVIA-LR (Contre les Maladies Chroniques pour un Vieillissement Actif en Languedoc Roussillon) to propose an operational definition of Active and Healthy Ageing including tools that may be used for this. The current paper describes the rationale and the process by which the aims of the meeting will be reached.
Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias
Publisher: BMJ
Date: 08-06-2021
Abstract: All categories included in the AT(N) classification can now be measured in plasma. However, their agreement with cerebrospinal fluid (CSF) markers is not fully established. A blood signature to generate the AT(N) classification would facilitate early diagnosis of patients with Alzheimer’s disease (AD) through an easy and minimally invasive approach. We measured Aβ, pTau181 and neurofilament light (NfL) in 150 plasma s les of the Sant Pau Initiative on Neurodegeneration cohort including patients with mild cognitive impairment, AD dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal participants. We classified participants in the AT(N) categories according to CSF biomarkers and studied the diagnostic value of plasma biomarkers within each category in idually and in combination. The plasma Aβ composite, pTau181 and NfL yielded areas under the curve (AUC) of 0.75, 0.78 and 0.88 to discriminate positive and negative participants in their respective A, T and N categories. The combination of all three markers did not outperform pTau181 alone (AUC=0.81) to discriminate A+T+ from A–T– participants. There was a moderate correlation between plasma Aβ composite and CSF Aβ1–42/Aβ1–40 (Rho=−0.5, p .001) and between plasma pTau181 and CSF pTau181 in the entire cohort (Rho=0.51, p .001). NfL levels in plasma showed high correlation with those in CSF (Rho=0.78, p .001). Plasma biomarkers are useful to detect the AT(N) categories, and their use can differentiate patients with pathophysiological evidence of AD. A blood AT(N) signature may facilitate early diagnosis and follow-up of patients with AD through an easy and minimally invasive approach.
Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer’s disease in adults with Down syndrome
Publisher: Springer Science and Business Media LLC
Date: 14-07-2021
DOI: 10.1038/S41467-021-24319-X
Abstract: Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer’s disease (AD) pathology with high accuracy in the general population. In this study, we investigated plasma p-tau181 as a biomarker of AD in in iduals with Down syndrome (DS). We included 366 adults with DS (240 asymptomatic, 43 prodromal AD, 83 AD dementia) and 44 euploid cognitively normal controls. We measured plasma p-tau181 with a Single molecule array (Simoa) assay. We examined the diagnostic performance of p-tau181 for the detection of AD and the relationship with other fluid and imaging biomarkers. Plasma p-tau181 concentration showed an area under the curve of 0.80 [95% CI 0.73–0.87] and 0.92 [95% CI 0.89–0.95] for the discrimination between asymptomatic in iduals versus those in the prodromal and dementia groups, respectively. Plasma p-tau181 correlated with atrophy and hypometabolism in temporoparietal regions. Our findings indicate that plasma p-tau181 concentration can be useful to detect AD in DS.
Relationship between genome and epigenome - challenges and requirements for future research
Publisher: Springer Science and Business Media LLC
Date: 18-06-2014
Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome
Publisher: American Medical Association (AMA)
Date: 08-2021
Editorial: Proteomics as a Tool for Biomarker and Drug Target Discovery: Improving the Diagnosis and Treatment of Neurodegenerative Diseases
Publisher: Frontiers Media SA
Date: 26-11-2020
Isolation of Exosomes and Microvesicles from Cell Culture Systems to Study Prion Transmission
Publisher: Springer New York
Date: 10-12-2016
DOI: 10.1007/978-1-4939-6728-5_11
Abstract: Extracellular vesicles (EVs) are composed of microvesicles and exosomes. Exosomes are small membrane vesicles (40-120 nm sized) of endosomal origin released in the extracellular medium from cells when multivesicular bodies fuse with the plasma membrane, whereas microvesicles (i.e., shedding vesicles, 100 nm to 1 μm sized) bud from the plasma membrane. Exosomes and microvesicles carry functional proteins and nucleic acids (especially mRNAs and microRNAs) that can be transferred to surrounding cells and tissues and can impact multiple dimensions of the cellular life. Most of the cells, if not all, from neuronal to immune cells, release exosomes and microvesicles in the extracellular medium, and all biological fluids including blood (serum lasma), urine, cerebrospinal fluid, and saliva contain EVs.Prion-infected cultured cells are known to secrete infectivity into their environment. We characterized this cell-free form of prions and showed that infectivity was associated with exosomes. Since exosomes are produced by a variety of cells, including cells that actively accumulate prions, they could be a vehicle for infectivity in body fluids and could participate to the dissemination of prions in the organism. In addition, such infectious exosomes also represent a natural, simple, biological material to get key information on the abnormal PrP forms associated with infectivity.In this chapter, we describe first a method that allows exosomes and microvesicles isolation from prion-infected cell cultures and in a second time the strategies to characterize the prions containing exosomes and their ability to disseminate the prion agent.
Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders
Publisher: Springer Science and Business Media LLC
Date: 08-06-2020
DOI: 10.1038/S41598-020-66090-X
Abstract: Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.
Plasma and CSF biomarkers for the diagnosis of Alzheimer's disease in adults with Down syndrome: a cross-sectional study
Publisher: Elsevier BV
Date: 10-2018
Carbon–concentration and carbon–climate feedbacks in CMIP6 models and their comparison to CMIP5 models
Publisher: Copernicus GmbH
Date: 18-08-2020
Abstract: Abstract. Results from the fully and biogeochemically coupled simulations in which CO2 increases at a rate of 1 % yr−1 (1pctCO2) from its preindustrial value are analyzed to quantify the magnitude of carbon–concentration and carbon–climate feedback parameters which measure the response of ocean and terrestrial carbon pools to changes in atmospheric CO2 concentration and the resulting change in global climate, respectively. The results are based on 11 comprehensive Earth system models from the most recent (sixth) Coupled Model Intercomparison Project (CMIP6) and compared with eight models from the fifth CMIP (CMIP5). The strength of the carbon–concentration feedback is of comparable magnitudes over land (mean ± standard deviation = 0.97 ± 0.40 PgC ppm−1) and ocean (0.79 ± 0.07 PgC ppm−1), while the carbon–climate feedback over land (−45.1 ± 50.6 PgC ∘C−1) is about 3 times larger than over ocean (−17.2 ± 5.0 PgC ∘C−1). The strength of both feedbacks is an order of magnitude more uncertain over land than over ocean as has been seen in existing studies. These values and their spread from 11 CMIP6 models have not changed significantly compared to CMIP5 models. The absolute values of feedback parameters are lower for land with models that include a representation of nitrogen cycle. The transient climate response to cumulative emissions (TCRE) from the 11 CMIP6 models considered here is 1.77 ± 0.37 ∘C EgC−1 and is similar to that found in CMIP5 models (1.63 ± 0.48 ∘C EgC−1) but with somewhat reduced model spread. The expressions for feedback parameters based on the fully and biogeochemically coupled configurations of the 1pctCO2 simulation are simplified when the small temperature change in the biogeochemically coupled simulation is ignored. Decomposition of the terms of these simplified expressions for the feedback parameters is used to gain insight into the reasons for differing responses among ocean and land carbon cycle models.
Related Organisations
Related Funding Activities
No related grants have been discovered for Sylvain Lehmann.