Luc Buee

Luc Buee
Université de Lille · Centre de Recherche Lille Neuroscience & Cognition (U1172)

Ph.D.

About

571
Publications
80,482
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
22,469
Citations
Introduction
Luc Buée is a French scientist (CNRS Research Director). Head of the Inserm laboratory « Alzheimer & Tauopathies » at the Jean-Pierre Aubert Research Centre, University of Lille, France. He has worked on Alzheimer disease and related disorders for more than twenty five years. He started his work on the role of proteoglycans in Alzheimer's disease with a PhD training at Mount Sinai Medical Center, NYC. He was then involved in the initial characterization of tau aggregates among neurodegenerative disorders. He has then developed experimental models to better understand tau aggregation and propagation. His group is currently working on the atypical Tau functions, the pathophysiological consequences of neurofibrillary degeneration in Alzheimer disease and Tauopathies. Luc Buée is also involved in different scientific advisory boards and operating committees in the field of AD. From 2012-2016, he was also a delegate at the Inserm Board for scientific evaluations in Neurosciences (CSS 6).Since Oct. 2017, he is the vice-president of the French Society for Neuroscience.

Publications

Publications (571)
Article
Full-text available
The molecular pathways underlying tau pathology–induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration. However, tau pathology may also result in the loss of specific physiological...
Article
Alzheimer's disease is characterized by the combined presence of amyloid plaques and tau pathology, the latter being correlated with the progression of clinical symptoms. Neuroinflammatory changes are thought to be major contributors to Alzheimer's disease pathophysiology, even if their precise role still remains largely debated. Notably, to what e...
Article
Full-text available
Tau is a central player in Alzheimer's disease (AD) and related Tauopathies, where it is found as aggregates in degenerating neurons. Abnormal post-translational modifications, such as truncation, are likely involved in the pathological process. A major step forward in understanding the role of Tau truncation would be to identify the precise cleava...
Article
Full-text available
In sporadic Tauopathies, neurofibrillary degeneration (NFD) is characterised by the intraneuronal aggregation of wild-type Tau proteins. In the human brain, the hierarchical pathways of this neurodegeneration have been well established in Alzheimer's disease (AD) and other sporadic tauopathies such as argyrophilic grain disorder and progressive sup...
Article
Full-text available
Nucleic acid protection is a substantial challenge for neurons, which are continuously exposed to oxidative stress in the brain. Neurons require powerful mechanisms to protect DNA and RNA integrity and ensure their functionality and longevity. Beside its well known role in microtubule dynamics, we recently discovered that Tau is also a key nuclear...
Article
Full-text available
Neurodegenerative disorders of the central nervous system (CNS) and brain traumatic insults are characterized by complex overlapping pathophysiological alterations encompassing neuroinflammation, alterations of synaptic functions, oxidative stress, and progressive neurodegeneration that eventually lead to irreversible motor and cognitive dysfunctio...
Article
Full-text available
Background: Pathogenic variants in the LRRK2 gene are a common monogenic cause of Parkinson's disease. However, only seven variants have been confirmed to be pathogenic. Objectives: We identified two novel LRRK2 variants (H230R and A1440P) and performed functional testing. Methods: We transiently expressed wild-type, the two new variants, or t...
Article
Full-text available
Brain administration of human platelet lysates (HPL) is an emerging biotherapy of neurodegenerative and traumatic diseases of the central nervous system (CNS). HPLs being prepared from pooled platelet concentrates (PCs) increasing viral risks, manufacturing processes should incorporate robust virus‐reduction treatments. We evaluated a 19±2‐nm virus...
Article
Increasing loss of structure and function of neurons and decline in cognitive function is commonly seen during the progression of neurologic diseases, although the causes and initial symptoms of individual diseases are distinct. This observation suggests a convergence of common degenerative features. In myotonic dystrophy type 1 (DM1), the expressi...
Article
Full-text available
Caffeine is the most consumed psychoactive substance worldwide. Strikingly, molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal-omics techniques. Our results revealed that chronic caffeine...
Article
Introduction: Few studies have attempted to evaluate the early efficacy of first-generation somatostatin analogs in somatotroph macroadenomas. Objective: To investigate the short-term efficacy of primary therapy with lanreotide 120 mg at one and three months on tumor shrinkage and ophthalmologic symptoms in newly diagnosed patients with acromegaly....
Article
Background: Few studies to date have attempted to measure serum anti-Müllerian hormone (AMH) levels in adult men, and solid references ranges have not yet been defined on a large cohort. Objective: In this study, we aimed to first establish the reference ranges for serum AMH and AMH-to-total testosterone ratio (AMH/tT) in adult males. Secondly, we...
Preprint
The accumulation of pathological Tau in the brain and cerebrospinal fluid (CSF) and its eventual increase in the blood are hallmarks of Alzheimer’s disease (AD). However, the mechanisms of Tau clearance from the brain to the periphery are not clear. We show here, using animal and cellular models as well as patient blood samples and post mortem brai...
Article
Full-text available
Several mutations on neuronal voltage-gated Ca2+ channels (VGCC) have been shown to cause neurological disorders and contribute to the initiation of epileptic seizures, migraines, or cerebellar degeneration. Analysis of the functional consequences of these mutations mainly uses heterologously expressed mutated channels or transgenic mice which mimi...
Article
Full-text available
Abstract Background: Few studies to date have attempted to measure serum anti-Müllerian hormone (AMH) levels in adult men, and solid references ranges have not yet been defined on a large cohort. Objective: In this study, we aimed to first establish the reference ranges for serum AMH and AMH-to-total testosterone ratio (AMH/tT) in adult males. Sec...
Article
Background Few studies to date have attempted to measure serum anti-Müllerian hormone (AMH) levels in adult men, and solid references ranges have not yet been defined on a large cohort. Objective In this study, we aimed to first establish the reference ranges for serum AMH and AMH-to-total testosterone ratio (AMH/tT) in adult males. Secondly, we i...
Article
Full-text available
Introduction: Few studies have attempted to evaluate the early efficacy of first-generation somatostatin analogs in somatotroph macroadenomas. Objective: To investigate the short-term efficacy of primary therapy with lanreotide 120 mg at one and three months on tumor shrinkage and ophthalmologic symptoms in newly diagnosed patients with acromega...
Article
Full-text available
With the expand of the population’s average age, the incidence of neurodegenerative disorders has dramatically increased over the last decades. Alzheimer disease (AD) which is the most prevalent neurodegenerative disease is mostly sporadic and primarily characterized by cognitive deficits and neuropathological lesions such as amyloid -β (Aβ) plaque...
Article
Full-text available
Alzheimer’s disease (AD) is the leading cause of dementia. While impaired glucose homeostasis has been shown to increase AD risk and pathological loss of tau function, the latter has been suggested to contribute to the emergence of the glucose homeostasis alterations observed in AD patients. However, the links between tau impairments and glucose ho...
Article
Full-text available
Myotonic dystrophy type 1 (DM1) is an RNA-dominant disease whose pathogenesis stems from the functional loss of muscleblind-like RNA-binding proteins (RBPs), which causes the formation of alternative-splicing defects. The loss of functional muscleblind-like protein 1 (MBNL1) results from its nuclear sequestration by mutant transcripts containing pa...
Article
Due to the pathophysiological complexity of Alzheimer's disease, multitarget approaches able to mitigate several pathogenic mechanisms are of interest. Previous studies have pointed to the neuroprotective potential of Doxycycline (Dox), a safe and inexpensive second-generation tetracycline. Dox has been particularly reported to slow down aggregatio...
Article
Introduction: Blood-based biomarkers are the next challenge for Alzheimer's disease (AD) diagnosis and prognosis. Methods: Mild cognitive impairment (MCI) participants (N = 485) of the BALTAZAR study, a large-scale longitudinal multicenter cohort, were followed-up for 3 years. A total of 165 of them converted to dementia (95% AD). Associations o...
Article
Full-text available
Tau proteins are known to be mainly involved in regulation of microtubule dynamics. Besides this function, which is critical for axonal transport and signal transduction, tau proteins also have other roles in neurons. Moreover, tau proteins are turned into aggregates and consequently trigger many neurodegenerative diseases termed tauopathies, of wh...
Article
Full-text available
Tau proteins aggregate into filaments in brain cells in Alzheimer’s disease and related disorders referred to as tauopathies. Here, we used fragments of camelid heavy-chain-only antibodies (VHHs or single domain antibody fragments) targeting Tau as immuno-modulators of its pathologic seeding. A VHH issued from the screen against Tau of a synthetic...
Preprint
Full-text available
Background Pathogenic variants in the LRRK2 gene are a common monogenic cause of Parkinson’s disease. However, only seven variants have been confirmed to be pathogenic. Objectives We identified two novel LRRK2 variants (H230R and A1440P) and performed functional testing. Methods We transiently expressed wildtype, the two new variants, or two know...
Article
Full-text available
Les vésicules extracellulaires (VE) sont libérées par une grande variété de cellules et contiennent des protéines, des ARN et des lipides, qui sont ainsi échangés entre ces cellules. Elles représentent donc un mode de communication intercellulaire majeur aussi bien en conditions physiologiques que pathologiques. C’est notamment le cas dans le systè...
Article
Full-text available
An extensive body of literature suggested a possible role of the microtubule-associated protein Tau in chromatin functions and/or organization in neuronal, non-neuronal, and cancer cells. How Tau functions in these processes remains elusive. Here we report that Tau expression in breast cancer cell lines causes resistance to the anti-cancer effects...
Article
Full-text available
Amyloid-β (Aβ) pathology transmission has been described in patients following iatrogenic exposure to compounds contaminated with Aβ proteins. It can induce cerebral Aβ angiopathy resulting in brain hemorrhages and devastating clinical impacts. Iatrogenic transmission of tau pathology is also suspected but not experimentally proven. In both scenari...
Article
La maladie d’Alzheimer est caractérisée du point de vue neuropathologique par des dépôts de protéine tau et de protéine bêta-amyloïde. Les modèles murins transgéniques de la maladie expriment l’une ou l’autre des protéines humaines mutée induisant leur dépôt. Ces modèles initialement développés pour l’étude mécanistique de la maladie permettent éga...
Article
Tauopathies are neurodegenerative diseases characterized by tau inclusions in brain cells. Seed-competent tau species have been suggested to spread from cell to cell in a stereotypical manner, indicating that this may involve a prion-like mechanism. Although the intercellular mechanisms of transfer are unclear, extracellular vesicles (EVs) could be...
Article
Full-text available
Studies supporting a strong association between tau deposition and neuronal loss, neurodegeneration, and cognitive decline have heightened the allure of tau and tau‐related mechanisms as therapeutic targets. In February 2020, leading tau experts from around the world convened for the first‐ever Tau2020 Global Conference in Washington, DC, co‐organi...
Article
Full-text available
Alzheimer's disease is the most common form of dementia characterized by intracellular aggregates of hyperphosphorylated Tau protein and extracellular accumulation of amyloid β (Aβ) peptides. We previously demonstrated that the purinergic receptor P2X7 (P2X7) plays a major role in Aβ-mediated neurodegeneration but the relationship between P2X7 and...
Article
Full-text available
Neuroinflammation in patients with Alzheimer’s disease (AD) and related mouse models has been recognized for decades, but the contribution of the recently described meningeal immune population to AD pathogenesis remains to be addressed. Here, using the 3xTg-AD model, we report an accumulation of interleukin-17 (IL-17)-producing cells, mostly γδ T c...
Article
Full-text available
Identifying which among several in cellulo pharmacological activities is necessary for the proper in vivo activity is essential for further drug development against Alzheimer's disease pathophysiological processes. An in-depth structure-activity relationship-based study has been carried out, and two molecules, named MAGS02-14 and PEL24-199, that sh...
Article
Full-text available
Tau pathology is instrumental in the gradual loss of neuronal functions and cognitive decline in tauopathies, including Alzheimer’s disease (AD). Earlier reports showed that adenosine metabolism is abnormal in the brain of AD patients while consequences remained ill-defined. Herein, we aimed at investigating whether manipulation of adenosine tone w...
Article
Full-text available
Traumatic brain injury leads to major brain anatomopathological damages underlined by neuroinflammation, oxidative stress and progressive neurodegeneration, ultimately leading to motor and cognitive deterioration. The multiple pathological events resulting from traumatic brain injury can be addressed not by a single therapeutic approach, but rather...
Article
Full-text available
Introduction: There is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures. Methods: We included 12,369 non-demented participants from eight population-based studies....
Article
Full-text available
The role played by microglia has taken the center of the stage in the etiology of Alzheimer's disease (AD). Several genome-wide association studies carried out on large cohorts of patients have indeed revealed a large number of genetic susceptibility factors corresponding to genes involved in neuroinflammation and expressed specifically by microgli...
Preprint
Full-text available
Alzheimer’s disease is characterized by lesions including extracellular amyloid-β plaques, intracellular tau accumulations, activated microglia around amyloid plaques and synaptic alterations that lead to cognitive impairments. Tau lesions occur in the form of tau-positive aggregates surrounding amyloid-β deposits leading to neuritic plaques, neuro...
Preprint
Full-text available
A structure-activity relationship has enabled us to identify two molecules, MAGS02-14 and PEL24-199, sharing a β-secretase modulatory effect but having or not a lysosomotropic activity, respectively. More importantly, MAGS02-14 and PEL24-199 only differ from each other by a single nitrogen atom. However, which of the lysosomotropic and/or β-secreta...
Preprint
Full-text available
Tau proteins aggregate into filaments in brain cells in Alzheimer's disease and related disorders referred to as tauopathies. Here, we used fragments of camelid heavy-chain-only antibodies (VHHs or single domain antibody fragments) targeting Tau as immuno-modulators of its pathologic seeding. A VHH issued from the screen against Tau of a synthetic...
Article
Les patients atteints d’une maladie d’Alzheimer (MA), dont une des lésions caractéristiques est la présence d’agrégats cérébraux de protéines Tau, présentent fréquemment des troubles de l’homéostasie glucidique. De manière intéressante, chez les patients atteints de MA, les agrégats de protéines Tau, conduisant à une perte de la fonction physiologi...
Article
In this study, we present the microfabrication and characterization of a transparent microelectrode array (MEA) system based on PEDOT:PSS for electrophysiology. The influence of the PEDOT:PSS electrode dimensions on the impedance was investigated and the stability over time under physiological environment was demonstrated. A very good transparency...
Article
Full-text available
Following publication of the original article [1], the authors reported that the author given names and family names had been transposed. The author names in this correction article are presented correctly.
Article
Full-text available
Alzheimer’s disease (AD) is characterized by the accumulation of the tau protein in neurons, neurodegeneration and memory loss. However, the role of non-neuronal cells in this chain of events remains unclear. In the present study, we found accumulation of tau in hilar astrocytes of the dentate gyrus of individuals with AD. In mice, the overexpressi...
Article
Recent studies indicate that anesthesia is likely to contribute to the development and exacerbation of neurodegenerative disorders such as Alzheimer’s disease (AD). Although it is well established that tau hyperphosphorylation is induced following anesthesia and is a major neuropathological hallmark of AD, the relationship between tau pathology and...
Article
Alzheimer’s disease is characterized by the extracellular accumulation of amyloid beta (Aß), intraneuronal formation of neurofibrillary tangles made of hyperphosphorylated tau and activated microglial cells, the innate immune cells of the brain. Activation of microglia by Aß or other DAMPs results in the assembly of the NLRP3 inflammasome consistin...
Preprint
Full-text available
Autosomal dominant cerebellar ataxia corresponds to a clinically and genetically heterogeneous group of neurodegenerative disorders that primarily affect the cerebellum. Here, we report the identification of the causative gene in spinocerebellar ataxia 21, an autosomal-dominant disorder previously mapped to chromosome 7p21.3-p15.1. This ataxia was...
Preprint
Full-text available
A variety of missense mutations and a stop mutation in the gene coding for transmembrane protein 240 (TMEM240) have been reported to be the causative mutations of spinocerebellar ataxia 21 (SCA21). We aimed to investigate the expression of TMEM240 protein in mouse brain at the tissue, cellular, and subcellular levels. Immunofluorescence labeling sh...
Preprint
Full-text available
Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease causing parkinsonian symptoms. Altered DNA methylation of the microtubule-associated protein tau gene correlates with the expression changes in Alzheimer's disease and Parkinson's disease brains. However, few studies examine the sequences beyond the constitutive pr...
Article
In Alzheimer’s disease, the tauopathy is known as a major mechanism responsible for the development of cognitive deficits. Early biomarkers of such affectations for diagnosis/stratification are crucial in Alzheimer’s disease research, and brain connectome studies increasingly show their potential establishing pathology fingerprints at the network l...
Preprint
Full-text available
Tau hyperphosphorylation favors the formation of neurofibrillary tangles and triggers the gradual loss of neuronal functions in tauopathies, including Alzheimer’s disease. Herein, we demonstrated that chronic treatment with an inhibitor (J4) of equilibrative nucleoside transporter 1 (ENT1), which plays a critical role in controlling adenosine homeo...
Article
Full-text available
A major goal in diseases is identifying a potential therapeutic agent that is cost-effective and can remedy some, if not all, disease symptoms. In Alzheimer's disease (AD), aggregation of hyperphosphorylated tau protein is one of the neuropathological hallmarks, and Tau pathology correlates better with cognitive impairments in AD patients than amyl...