Publications by authors named "Michel Bottlaender"

Objectives: Resective surgery in drug-resistant focal epilepsy (DRFE) requires extensive evaluation to localize the epileptogenic zone (EZ). When non-invasive phase 1 assessments (electroencephalography, EEG; magnetic resonance imaging, MRI; and F-Fluorodeoxyglucose-positron emission tomography, [F]FDG-PET) are inconclusive for EZ localization, invasive investigations such as stereo-EEG (SEEG) are necessary. Epileptogenicity maps (Ems) visualize the EZ using SEEG-identified ictal high-frequency oscillations (iHFOs).

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  • TSPO (translocator protein) is a mitochondrial protein found in microglia and is used as a neuroinflammation marker in PET scans for Alzheimer's disease (AD).
  • This study aims to better understand the microglial phenotype linked to TSPO expression by analyzing human brain samples from different stages of AD.
  • The findings indicate that TSPO is primarily associated with phagocytic microglia (specifically CD68), suggesting a role in ongoing neurodegeneration in Alzheimer's disease.
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Background: Iron accumulates in the brain during aging and is the focus of intensive research as an abnormal load, particularly in Deep Gray Matter (DGM), is related to neurodegeneration. Magnetic Resonance Imaging (MRI) metrics such as Quantitative Susceptibility Mapping (QSM) and apparent transverse relaxation rate can be used to follow up iron . While the influence of age and sex on iron levels has already been reported, a careful consideration of neuronal risk factors, as well as for an enhanced sensitivity, is needed to define the normal evolution.

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We have previously developed seven fluorinated analogues of A-836339 as new PET tracers for cannabinoid type 2 receptor (CBR) imaging, among which ()--(3-(2-(2-[F]fluoroethoxy)ethyl)-4,5-dimethylthiazol-2(3)-ylidene)-2,2,3,3-tetramethylcyclopropane-1-carboxamide ([F]FC0324) displayed high affinity and selectivity for CBR in healthy rats. In the present study, we have further evaluated the imaging and metabolic properties of [F]FC0324 in a rat model of human CBR overexpression in the brain (AAV-CB) and in non-human primates (NHPs). Autoradiography with AAV-CB rat brain sections exhibited a signal of [F]FC0324 8-fold higher in the ipsilateral region than in the contralateral region.

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The understanding of the human brain is one of the main scientific challenges of the twenty-first century. In the early 2000s, the French Atomic Energy Commission launched a program to conceive and build a human magnetic resonance imaging scanner operating at 11.7 T.

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Introduction: Typical Alzheimer's disease (AD) and limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE) are two neurodegenerative diseases that present with a similar initial amnestic clinical phenotype but are associated with distinct proteinopathies.

Methods: We investigated white matter (WM) fiber bundle alterations, using fixel-based analysis, a state-of-the-art diffusion magnetic resonance imaging model, in early AD, presumed LATE, and controls. We also investigated regional cortical atrophy.

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Introduction: Recent evidence suggests the blood-to-brain influx rate ( ) in imaging as a promising biomarker of blood-brain barrier () permeability alterations commonly associated with peripheral inflammation and heightened immune activity in the brain. However, standard compartmental modeling quantification is limited by the requirement of invasive and laborious procedures for extracting an arterial blood input function. In this study, we validate a simplified blood-free methodologic framework for estimation by fitting the early phase tracer dynamics using a single irreversible compartment model and an image-derived input function ().

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Article Synopsis
  • - Mitochondrial dysfunctions are prominent in Alzheimer's disease (AD), and their effects on peripheral cells in patients are not well understood, prompting this study focusing on fibroblasts from both healthy volunteers and AD patients at different stages.
  • - Researchers examined mitochondrial structure, function, and mitophagy, correlating findings with cognitive tests (MMSE, CDR-SOB), amyloid beta plaque levels, and peripheral amyloid precursor protein fragments.
  • - The study found mitochondrial alterations and dysfunctions linked to cognitive decline and other AD-related symptoms, highlighting the importance of peripheral cells in AD research.
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The cautious optimism following recent anti-amyloid therapeutic trials for Alzheimer's disease (AD) provides a glimmer of hope after years of disappointment. Although these encouraging results represent discernible progress, they also highlight the need to enhance further the still modest clinical efficacy of current disease-modifying immunotherapies. Here, we highlight crucial milestones essential for advancing precision medicine in AD.

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  • The study aimed to evaluate the relationship between oxygen supply and myelin damage in the brain by simultaneously measuring myelin and cerebral blood flow (CBF) using dynamic [11C]PiB PET scans.* -
  • Eight healthy subjects underwent two PET scans to compare three quantitative analysis methods for CBF and myelin content, focusing on the impact of region size and assessing reproducibility and intercorrelations between metrics.* -
  • Results indicated that the SRTM2 method was the most reliable for CBF measurement in white matter, showing lower blood flow in white compared to grey matter and revealing important interactions between region size and measurement reliability.*
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Background: The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer's disease (AD). Little is known about LC and NBM alteration in limbic-predominant age-related TDP-43 encephalopathy (LATE) and frontotemporal dementia (FTD). The aim of the present study is to investigate in vivo LC and NBM integrity in patients with suspected-LATE, early-amnestic AD and FTD in comparison with controls.

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Numerous studies suggest that blood-brain barrier (BBB) dysfunction may contribute to the progression of Alzheimer's disease (AD). Clinically available neuroimaging methods are needed for quantitative "scoring" of BBB permeability in AD patients. [F]2-fluoro-2-deoxy-sorbitol ([F]FDS), which can be easily obtained from simple chemical reduction of commercial [F]2-fluoro-2-deoxy-glucose ([F]FDG), was investigated as a small-molecule marker of BBB permeability, in a pre-clinical model of AD using in vivo PET imaging.

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Among opioids, buprenorphine presents a favorable safety profile with a limited risk of respiratory depression. However, fatalities have been reported when buprenorphine is combined to a benzodiazepine. Potentiation of buprenorphine interaction with opioid receptors (ORs) with benzodiazepines, and/or vice versa, is hypothesized to explain this drug-drug interaction (DDI).

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Background And Objectives: Translocator protein 18 kDa (TSPO) PET imaging is used to monitor glial activation. Recent studies have proposed TSPO PET as a marker of the epileptogenic zone (EZ) in drug-resistant focal epilepsy (DRFE). This study aims to assess the contributions of TSPO imaging using [F]DPA-714 PET and [F]FDG PET for localizing the EZ during presurgical assessment of DRFE, when phase 1 presurgical assessment does not provide enough information.

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The 18kD translocator protein (TSPO) is used as a positron emission tomography (PET) target to quantify neuroinflammation in patients. In Alzheimer's disease (AD), the cerebellum is the pseudo-reference region for comparison with the cerebral cortex due to the absence of AD pathology and lower levels of TSPO. However, using the cerebellum as a pseudo-reference region is debated, with other brain regions suggested as more suitable.

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Article Synopsis
  • The study focuses on a protein called TSPO that can help doctors see inflammation in the brain using a special imaging test called PET.
  • Researchers wanted to understand how well TSPO PET works for different brain disorders and at different stages of those disorders.
  • They reviewed a lot of research (156 studies!) involving both healthy people and patients to compare how TSPO PET results differed across various illnesses.
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The hippocampal subfields, pivotal to episodic memory, are distinct both in terms of cyto- and myeloarchitectony. Studying the structure of hippocampal subfields is crucial to understand volumetric trajectories across the lifespan, from the emergence of episodic memory during early childhood to memory impairments found in older adults. However, segmenting hippocampal subfields on conventional MRI sequences is challenging because of their small size.

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Aim: Buprenorphine mainly acts as an agonist of mu-opioid receptors (mu-OR). High dose buprenorphine does not cause respiratory depression and can be safely administered to elicit typical opioid effects and explore pharmacodynamics. Acute buprenorphine, associated with functional and quantitative neuroimaging, may therefore provide a fully translational pharmacological challenge to explore the variability of response to opioids .

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Background: Monitoring the progression of Tau pathology makes it possible to study the clinical diversity of Alzheimer's disease. In this 2-year longitudinal PET study, we aimed to determine the progression of [F]-flortaucipir binding and of cortical atrophy, and their relationships with cognitive decline.

Methods: Twenty-seven AD patients at the mild cognitive impairment/mild dementia stages and twelve amyloid-negative controls underwent a neuropsychological assessment, 3 T brain MRI, and [F]-flortaucipir PET imaging (Tau1) and were monitored annually over 2 years with a second brain MRI and tau-PET imaging after 2 years (Tau2).

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Objective: To determine the prognostic value of persisting neuroinflammation in multiple sclerosis (MS) lesions, we developed a 18 kDa-translocator-protein-positron emission tomography (PET) -based classification of each lesion according to innate immune cell content and localization. We assessed the respective predictive value of lesion phenotype and diffuse inflammation on atrophy and disability progression over 2 years.

Methods: Thirty-six people with MS (disease duration 9 ± 6 years; 12 with relapsing-remitting, 13 with secondary-progressive, and 11 with primary-progressive) and 19 healthy controls (HCs) underwent a dynamic [ F]-DPA-714-PET.

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Early markers are needed for more effective prevention of Alzheimer's disease. We previously showed that individuals with Alzheimer's disease have decreased plasma DYRK1A levels compared to controls. We assessed DYRK1A in the plasma of cognitively healthy elderly volunteers, individuals with either Alzheimer's disease (AD), tauopathies or Down syndrome (DS), and in lymphoblastoids from individuals with DS.

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Morphological alterations of the endosomal compartment have been widely described in post-mortem brains from Alzheimer's disease (AD) patients and subjects with Down syndrome (DS) who are at high risk for AD. Immunostaining with antibodies against endosomal markers such as Early Endosome Antigen 1 (EEA1) revealed increased size of EEA1-positive puncta. In DS, peripheral cells such as peripheral blood mononuclear cells (PBMCs) and fibroblasts, share similar phenotype even in the absence of AD.

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Introduction: Application of MRI in clinical routine mainly addresses structural alterations. However, pathological changes at a cellular level are expected to precede the occurrence of brain atrophy clusters and of clinical symptoms. In this context, Na-MRI examines sodium changes in the brain as a potential metabolic parameter.

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Organic Anion-Transporting Polypeptides (OATPs) are known to control the liver uptake of many drugs. Non-hepatic expression of OATPs has been reported although functional importance for whole-body pharmacokinetics (WBPK) remains unknown. Glyburide is a well described substrate of several hepatic and non-hepatic OATPs.

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