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Introduction
Luc Buée is a French scientist (CNRS Research Director). Head of the Inserm laboratory "Lille Neuroscience & Cognition", University of Lille, France.
He is an expert on tau proteins and tauopathies and member of different scientific committtee programs and scientific advisory boards.
He was President of the French Society for Neuroscience (2019-2021).
He is the Chair of the Eurotau meeting series (https://eurotau.fr ).
He is a foreign member of the Royal Academy of Medicine of Belgium.
Publications
Publications (630)
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...
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...
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...
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...
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...
Background
Current AT(N) stratification for Alzheimer’s disease (AD) accounts for complex combinations of amyloid (A), tau proteinopathy (T) and neurodegeneration (N) signatures. Understanding the transition between these different stages is a major challenge, especially in view of the recent development of disease modifying therapy.
Methods
This...
Microglial cells are the phagocytic cells of the brain that under physiological conditions participate in brain homeostasis and surveillance. Under pathogenic states, microglia undergoes strong morphological and transcriptional changes potentially leading to sustained neuroinflammation, brain damage, and cognitive disorders. Postnatal and adult Zik...
Background
The burgeoning field of regenerative medicine has significantly advanced with recent findings on biotherapies using human platelet lysates (HPLs), derived from clinical-grade platelet concentrates (PCs), for treating brain disorders. These developments have opened new translational research avenues to explore the neuroprotective effects...
Selective degradation of pathological protein aggregates while sparing monomeric forms is of major therapeutic interest. The E3 ligase tripartite motif–containing protein 21 (TRIM21) degrades antibody-bound proteins in an assembly state–specific manner due to the requirement of TRIM21 RING domain clustering for activation, yet effective targeting o...
INTRODUCTION
We investigated the link between habitual caffeine intake with memory impairments and cerebrospinal fluid (CSF) biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients.
METHODS
MCI (N = 147) and AD (N = 116) patients of the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) cohort reported...
Adenosine is an ubiquitous neuromodulator that ensures cerebral homeostasis. It exerts numerous functions through the activation of G-protein-coupled adenosine receptors (ARs), in particular A 1 (A 1 R) and A 2A (A 2A R) receptors. Interestingly, A 2A R levels are upregulated in cortical and hippocampal regions in several pathological conditions su...
Early pathological upregulation of adenosine A2A receptors (A2ARs), one of the caffeine targets, by neurons is thought to be involved in the development of synaptic and memory deficits in Alzheimer’s disease (AD) but mechanisms remain ill-defined. To tackle this question, we promoted a neuronal upregulation of A2AR in the hippocampus of APP/PS1 mic...
Caffeine consumption outcomes on Amyotrophic Lateral Sclerosis (ALS) including progression, survival and cognition remain poorly defined and may depend on its metabolization influenced by genetic variants. 378 ALS patients with a precise evaluation of their regular caffeine consumption were monitored as part of a prospective multicenter study. Demo...
Human platelet lysates (HPLs) from allogeneic platelet concentrates (PCs) are biomaterials, which are rich in various trophic factors, increasingly used in regenerative medicine and biotherapy. Understanding how preparation methods influence the HPL protein profile, biological function, and clinical outcomes is crucial. Our study sheds light on the...
Mitochondria dysfunctions and mitophagy failure have been associated with several Alzheimer’s disease (AD) related molecular actors including amyloid beta (Aβ) and recently the amyloid precursor protein-C terminal fragments (APP-CTFs). The efficacy of the mitophagy process in neurons relies on regulated mitochondrial transport along axons involving...
Background
Among plasma biomarkers for Alzheimer’s disease (AD), pTau181 and pTau217 are the most promising. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors.
Method
pTau181 and pTau217 were quantified using, Quanterix and ALZpath...
While the double helical structure has long been its iconic representation, DNA is structurally dynamic and can adopt alternative secondary configurations. Specifically, guanine‐rich DNA sequences can fold in guanine quadruplexes (G4) structures. These G4 play pivotal roles as regulators of gene expression and genomic stability, and influence prote...
We investigated the link between habitual caffeine intake with memory deficits and CSF AD biomarkers in Mild cognitive impairment (MCI) and Alzheimer s Disease (AD) patients.
MCI (N=147) and AD (N=116) patients of the BALTAZAR longitudinal cohort reported their caffeine intake using a dedicated survey and were followed-up for 3 years. Associations...
The transcellular propagation of the aberrantly modified protein tau along the functional brain network is a key hallmark of Alzheimer's disease and related tauopathies. Inoculation-based tau propagation models can recapitulate the stereotypical spread of tau and reproduce various types of tau inclusions linked to specific tauopathy, albeit with va...
Prion-like spread of disease-specific tau conformers is a hallmark of all tauopathies. A 19-residue probe peptide containing a P301L mutation and spanning the R2/R3 splice junction of tau folds and stacks into seeding-competent fibrils and induces aggregation of 4R, but not 3R tau. These tau peptide fibrils propagate aggregated intracellular tau ov...
Alzheimer’s disease (AD) progression and pathology show pronounced sex differences, but the factors driving these remain poorly understood. To gain insights into early AD-associated molecular changes and their sex dependency for tau pathology in the cortex, we performed single-cell RNA-seq in the THY-Tau22 AD mouse model. By examining cell type-spe...
The use of variable domain of the heavy-chain of the heavy-chain-only antibodies (VHHs) as disease-modifying biomolecules in neurodegenerative disorders holds promises, including targeting of aggregation-sensitive proteins. Exploitation of their clinical values depends however on the capacity to deliver VHHs with optimal physico-chemical properties...
Background and Purpose: Tau pathology is instrumental in the gradual loss of neuronal functions and cognitive decline in tauopathies, including Alzheimer’s disease (AD). Adenosine homeostasis is essential to brain metabolism and plasticity but the link to Tau remained ill-defined. Herein, we aimed at investigating whether modulating adenosine tone,...
Objectives
We sought to compare two of the most promising plasma biomarkers for Alzheimer disease: pTau181 and pTau217.
Methods
pTau181 and pTau217 were quantified using SIMOA Quanterix and ALZpath assays in the well characterized prospective multicentre BALTAZAR cohort of mild cognitive impairment (MCI) participants.
Results
Among MCI participants...
INTRODUCTION
The pace of innovation has accelerated in virtually every area of tau research in just the past few years.
METHODS
In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co‐organized and co‐sponsored by the Alzheimer's Association,...
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β plaques, aggregation of hyperphosphorylated tau (pTau), and microglia activation. Galectin-3 (Gal3) is a β-galactoside-binding protein that has been implicated in amyloid pathology. Its role in tauopathy remains enigmatic. Here, we showed that Gal3 was upregulated in the mic...
Early-life exposure to high-fat diets (HF) can program metabolic and cognitive alterations in adult offspring. Although the hippocampus plays a crucial role in memory and metabolic homeostasis, few studies have reported the impact of maternal HF on this structure. We assessed the effects of maternal HF during lactation on physiological, metabolic,...
Early-life exposure to high-fat diet (HF) can program metabolic and cognitive alterations in adult offspring. Although the hippocampus plays a crucial role in memory and metabolic homeostasis, few studies reported the impact of maternal HF on this structure. We assessed the effects of maternal HF during lactation on physiological, metabolic and cog...
Frontotemporal lobar degeneration with tau (FTLD-tau) is a group of tauopathies that underlie ∼50% of frontotemporal lobar degeneration (FTLD) cases. Identification of genetic risk variants related to innate/adaptive immunity have highlighted a role for neuroinflammation and neuroimmune interactions in FTLD. Studies have shown microglial and astroc...
The term 'endemic parkinsonism' refers to diseases that manifest with a dominant parkinsonian syndrome, which can be typical or atypical, and are present only in a particular geographically defined location or population. Ten phenotypes of endemic parkinsonism are currently known: three in the Western Pacific region; two in the Asian-Oceanic region...
Prion-like spread of disease-specific tau conformers is a hallmark of all tauopathies. A 19-residue probe peptide containing a P301L mutation and spanning the R2/R3 splice junction of tau, folds and stacks into seeding-competent fibrils and induces aggregation of 4R, but not 3R tau. These tau peptide fibrils propagate aggregated intracellular tau o...
Mitochondria dysfunctions and mitophagy failure have been associated with several Alzheimer’s disease (AD) related molecular actors including amyloid beta (Aβ) and recently the amyloid precursor protein-C terminal fragments (APP-CTFs). The efficacy of the mitophagy process in neurons relies on regulated mitochondrial transport along axons involving...
The use of VHHs (Variable domain of the Heavy-chain of the Heavy-chain-only antibodies) as disease-modifying biomolecules in neurodegenerative disorders holds promises including to target aggregation-sensitive proteins. Exploitation of their clinical values dependents however on the capacity to deliver VHHs with optimal physico-chemical properties...
Microelectrode Arrays (MEAs) are popular tools for in vitro extracellular recording. They are often optimized by surface engineering to improve affinity with neurons and guarantee higher recording quality and stability. Recently, PEDOT:PSS has been used to coat microelectrodes due to its good biocompatibility and low impedance, which enhances neura...
Citation: Perbet, R.; Zufferey, V.; Leroux, E.; Parietti, E.; Espourteille, J.; Culebras, L.; Perriot, S.; Du Pasquier, R.; Bégard, S.; Deramecourt, V.; et al. Tau Transfer via Extracellular Vesicles Disturbs the Astrocytic Mitochondrial System. Cells 2023, 12, 985. https://doi.org/10.3390/ cells12070985 Academic Editors: Abstract: Tauopathies are...
Recently, the development of electronic devices to extracellularly record the simultaneous electrical activities of numerous neurons has been blooming, opening new possibilities to interface and decode neuronal activity. In this work, we tested how the use of EDOT electropolymerization to tune post-fabrication materials could optimize the cell/elec...
The progress in Alzheimer’s disease (AD) treatment suggests a combined therapeutic approach targeting the two lesional processes of AD, which include amyloid plaques made of toxic Aβ species and neurofibrillary tangles formed of aggregates of abnormally modified Tau proteins. A pharmacophoric design, novel drug synthesis, and structure-activity rel...
Tauopathies are neurodegenerative disorders involving the accumulation of tau isoforms in cell subpopulations such as astrocytes. The origins of the 3R and 4R isoforms of tau that accumulate in astrocytes remain unclear.
Extracellular vesicles (EVs) were isolated from primary neurons overexpressing 1N3R or 1N4R tau or from human brain extracts (pro...
Recent reports suggested a role for microtubules in double-strand-DNA break repair. We herein investigated the role of the microtubule-associated protein Tau in radio- and chemotherapy. Noticeably, a lowered expression of Tau in breast cancer cell lines resulted in a significant decrease in mouse-xenograft breast tumor volume after doxorubicin or X...
Background
Zika virus (ZIKV) infection at postnatal or adult age can lead to neurological disorders associated with cognitive defects. Yet, how mature neurons respond to ZIKV remains substantially unexplored.
Methods
The impact of ZIKV infection on mature neurons and microglia was analyzed at the molecular and cellular levels, in vitro using immun...
Multiple lines of evidence have linked oxidative stress, tau pathology and neuronal cell cycle re-activation to Alzheimer’s disease (AD). While a prevailing idea is that oxidative stress-induced neuronal cell cycle reactivation acts as an upstream trigger for pathological tau phosphorylation, others have identified tau as an inducer of cell cycle a...
Adenosine signals through four distinct G protein-coupled receptors that are located at various synapses, cell types and brain areas. Through them, adenosine regulates neuromodulation, neuronal signaling, learning and cognition as well as the sleep-wake cycle, all strongly impacted in neurogenerative disorders, among which Alzheimer's Disease (AD)....
Objective:
Tau ablation has a protective effect in epilepsy due to inhibition of the hyperexcitability/hypersynchrony. Protection may also occur in transgenic models of Alzheimer's disease by reducing the epileptic activity and normalizing the excitation/inhibition imbalance. However, it is difficult to determine the exact functions of tau, becaus...
The rationale to define the biological and molecular parameters derived from structure–activity relationships (SAR) is mandatory for the lead selection of small drug compounds. Several series of small molecules have been synthesized based on a computer-assisted pharmacophore design derived from two series of compounds whose scaffold originates from...
Objectif
Étudier l’efficacité à un et trois mois d’un traitement en première intention par lanréotide 120 mg sur la réduction du volume tumoral (VT) et l’amélioration des atteintes ophtalmologiques chez des patients nouvellement diagnostiqués d’acromégalie.
Patients et méthodes
Dans cette étude monocentrique, 21 patients atteints d’acromégalie de...
Objectif
Nous avons d’abord cherché à établir l’intervalle de référence pour les concentrations sériques d’AMH chez des hommes adultes. Deuxièmement, nous avons étudié la relation entre les concentrations sériques d’AMH et les gonadotrophines, la testostérone totale ainsi que les paramètres spermatiques.
Patients et méthodes
Au total, 578 hommes a...
At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction-...
Neurofibrillary tangles (NFT), a neuronal lesion found in Alzheimer's disease (AD), are composed of fibrillary aggregates of modified forms of tau proteins. The propagation of NFT follows neuroanatomical pathways suggesting that synaptically connected neurons could transmit tau pathology by the recruitment of normal tau in a prion-like manner. More...
Alzheimer's disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Three types of tau lesions occur in the form of neuropil threads, neurofibrillary tangles, and neuritic plaques i.e. tau aggregates within neurites surrounding Aβ deposits. The ca...
Brain administration of human platelet lysates (HPL) is a potential emerging biotherapy of neurodegenerative and traumatic diseases of the central nervous system. HPLs being prepared from pooled platelet concentrates, thereby increasing viral risks, manufacturing processes should incorporate robust virus‐reduction treatments. We evaluated a 19 ± 2‐...
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...
Alzheimer’s disease is the most frequent form of dementia in aging population and is presently the world’s sixth largest cause of mortality. With the advancement of therapies, several solutions have been developed such as passive immunotherapy against these misfolded proteins, thereby resulting in the clearance. Within this segment, encapsulated ce...
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...
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...
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...
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....
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...
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...
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...
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...
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...
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...