Alzheimer
and Tauopathies

Presentation

“Alzheimer & Tauopathies” Tean  belongs to the “Lille Neuroscience & Cognition” and is located Lille, France.

Our team is interested in pathophysiological mechanisms leading to dementia and is composed of 16 permanent researchers: full time research scientists, professors and associate professors and clinicians. We also welcome postdoctoral fellows and MSc/PhD students. Our work focuses on Tau, protein involved in the physiopathology of Alzheimer’s disease and related disorders referred to as Tauopathies, going from the gene to the clinic and from basic research to biomedical application.

“Alzheimer & Tauopathies” team is interested in molecular and pathophysiological mechanisms of Tau pathophysiology. Our main contribution has been on the characterization of neurodegenerative disorders with dysfunction in Tau metabolism (expression, splicing, etc.) and the development of experimental models. We also demonstrated that Tau proteins are biomarkers of these disorders and correlated to neuronal death.

Our current research should lead to new diagnostic and therapeutic strategies of Alzheimer’s disease and related disorders. To the level of the etiopathogenesis of Alzheimer’s disease, the understanding of the relationships between amyloid pathology and Tau pathology is our main goal. Any molecular actors potentially involved in one of these pathways are evaluated in our experimental “humanized” models, as well as the related pharmacological aspects.

NEWS

hippocampe-Alzheimer-degenerescences-neurofibrillaires

Anti-pTau labeling of neurofibrillary degeneration in the hippocampus in a patient with Alzheimer’s disease.

 

VIDEO

Alzheimer’s disease: the challenges of research deciphered by 3 researchers supported by the FRM

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Researchers

DIRECTOR
Luc Buée, PhD.

CNRS research professor.
Head of the “Alzheimer & Tauopathies” team.
Director of the Lille Neuroscience & Cognition Research Center.
University of Lille, Faculty of Medicine.
Research :
Alzheimer & Tauopathies.

David Blum.
Inserm Research Professor.

Adjunct Professeur Taipei Medical University(Taïwan).
University of Lille, Faculty of Medicine.
Research :
Cerebral Homeostasis, Adenosine and its receptors, Metabolism, insulin resistance, neuroinflammation.
Methods: Animal models, behaviour, confocal microscopy, transcriptomics.

Marie-Christine Galas, PhD.
CNRS Research Professor.

University of Lille, School of Medicine.
Research: Nuclear tau, tau and genome integrity, tau and epigenomics.

Nicolas Sergeant, PhD.
Inserm research professor.

University of Lille, Faculty of Medicine
Research :
Pathophysiology of Tauopathies, biomarkers & new therapeutic targets.

Associate Professors/Professors – University-Associated

Dr. Valérie Buée-Scherrer, PhD.
Associate Professor (HDR-Docent)
University Artois, School of Sciences, Lens, France.
Teaching: Cell Biology.
Research : Molecular characterization of brain lesions found in neurodegenerat disorders. Studies in human and aivenimal models.
Methods: Biochemistry, Cell biology,  Molecular Biology, Immunohistochemistry.
Dr. Morvane Colin, PhD.
Associate Professor (HDR-Docent)
University of Lille, Faculty of Medicine.
Teaching: Cell Biology, Gene therapy & vectorology.
Research: “Tau spreading” Cell to cell transfer process; immunotherapy anti-tau, neuronal network.
Dedicated tools: Viral vectors, primary cultures, microfluidic, MEA, rodent model, animal models & intracranial delivery.
Dr. Sophie Halliez, PhD.
Associate Professor – Chair of excellence Inserm.
University of Lille, Faculty of Medicine.
Teaching : Molecular and cell neurobiology.
Research : Experimental models, physiological et pathological neural networks, cell mechanisms in tauopathies.
Methods :  Multielectrode arrays, microfluidics and neurobiology
Dr. Malika Hamdane, PhD.
Professor of Cell Biology (HDR-Docent).
University of Lille, Faculty of Medicine.
Teaching: Cell Biology, Biochemistry, Neuroscience.
Research: “Truncated Tau species”. The role in Alzheimer’s Disease and therapeutic and diagnosis applications.
Dr. Bruno Lefebvre, PhD.
Associate Professor (HDR).
University of Lille, Faculty of Medicine.
Teaching: Biochemistry, molecular and cell biology, epigenetics.
Research: Tau and nucleic acids.

Dr. Didier Vieau, PhD.
Professor of Physiology.
University of Lille, Faculty of “Sciences et Technologies”.
Teaching: Physiology and endocrinology.
Research : Short- and long-term influences of the perinatal environment on the programming of the stress response and chronic adult diseases such as obesity, diabetes and Alzheimer disease.

Associate Professors and Professors
University & Hospital-Associated

Prof. Vincent Deramecourt, MD, PhD.
professor of histology – Hospital Biologist.
University of Lille, Faculty of Medicine.
Teaching: : Anatomo-pathology, Histology, Dean's Assessor for PACES.
Research : Biomarkers of dementias - Clinical correlation.
Hospital activities: Neurologist - Neuropathologist.
Dr. Claire-Marie Dhaenens, PharmD, PhD, HDR, MCU-PH
University of Lille, Faculty of Medicine.
Research : Involved in genetics and epigenomics of Tauopathies and neurodegenerative disorders. Investigation of the MAPT gene regulation (alternative splicing, alternative promoter usage, transcription…) to explain the differential expression of Tau proteins in human brain and in experimental models.
Dr. Thibaud Lebouvier, MD, PhD.
Associate Professor – Hospital Biologist.
University of Lille, Faculty of Medicine.
Research : Frontotemporal lobar degenerations.
Hospital duties:  Neurologist.
Prof. Bernard Sablonnière, MD, PhD.
Professor, Hospital Biologist.
University of Lille, Faculty of Medicine.
Teaching: Biochemistry and molecular biology.
Research: Epigenomics, spino-cerebellar ataxia.
Hospital duties: Neurobiology, genetic diagnosis, biomarkers of dementia.
Dr Susanna Schraen-Maschke, PharmD, PhD, HDR, MCU-PH
University of Lille, Faculty of Medicine.
Research: Involved in the translational development and evaluation of biomarkers of Alzheimer’s disease in human biological fluids. Samples come from french national cohorts of patients, and on samples of the Lille University Hospital care. The aim is to evaluate their interest for diagnosis and prognosis of dementia.
Hospital duties : Biochemistry and Biomarkers of Dementias.
Dr Vincent Huin, MD, PhD, MCU-PH
University of Lille, Faculty of Medicine.
Research : Epigénomique des maladies neurodégénératives. Maladies à expansions de triplets
Hospital duties : Biochemistry and Genetics of Neurodegenerative Diseases.
 Dr Marie Dubar, M.D, Ph.D, MCU-PH
Université de Lille, Faculté de Médecine.

Research support staff

 Séverine Bégard
Inserm engineer
 Thomas Bouillet
Ingénieur d'Etude, CDD
 Anaïs Poncet
Ingénieure Hospitalière, CDD
 Emilie Faivre
University of Lille engineer
 Raphaëlle Caillierez
University of Lille engineer
 Sébastien Carrier
University of Lille technician
 Bryan Thiroux,
Engineers Assistant, CDD
 Sabiha Eddarkaoui
University of Lille engineer
 Thomas Comptdaer
University of Lille technician
 Florian Vermon
Engineers Assistant, CDD


Post Doctoral Researchers

 Carvalho Kevin, PhD
 Sayed Rassul Muhammed, PhD
 Guedjdal Sarah


Doctoral students

 Nebie Ouada
 Perbet Romain, AHU
 Tautou Marie
 Rico Thomas
 Sousa  Cristiano
 Pinheiro Werner
 Denechaud Marine
 Leroux Elodie
 Leroy Melanie
 Coku Ilda
 Zejneli Orgeta
 Kraiem Sarra
 Montmasson Claire
 Gauvrit Thibaut
 Benderradji Hamza

Alumni

  • BAUD Catherine, PhD
  • GOMEZ-MURCIA Victoria, PhD
  • MERIAUX Céline, PhD
  • SCHIRMER Claire, PhD
  • VINDTDEUX Valérie, PhD
  • ALBERT Marie, PhD
  • DANIS Clément, PhD
  • ERDUAL Edmone, PhD
  • EVRARD Caroline, PhD
  • GILLES, Mélissa, PhD
  • HOMA Mégane, PhD
  • ALVES-PIRES Claire, PhD
  • ANDO Kunie, PhD
  • BELARBI Karim, PhD
  • BOMBOIS Stéphanie, MD, PhD
  • BRETTEVILLE Alexis, PhD
  • BROUILLETTE Jonathan, PhD
  • BURNOUF Sylvie, PhD
  • BUSSIERE Thierry, PhD
  • CAILLET-BOUDIN Marie-Laure, PhD
  • CARPENTIER Céline, PhD
  • CELLAI Lucrezia, PhD
  • CHARTIER-HARLIN Marie-Christine, PhD
  • CHAUFERLIER Alban, PhD
  • DAVID Jean-Philippe, MD, PhD
  • DELACOURTE André, PhD
  • DELAY Charlotte, PhD
  • DELOBEL Patrice, PhD
  • DELPLANQUE Jérôme, PhD
  • DERISBOURG Maxime, PhD
  • DOURLEN Pierre, PhD
  • DUJARDIN Simon, PhD
  • DUPONT-WALLOIS Lætitia, PhD
  • FERNANDEZ-GOMEZ Francisco J, PhD
  • FERREIRA Stéphanie, PhD
  • FERRETTI Roberta, PhD
  • FLAMENT Stéphane, PhD
  • GELE Patrick, PhD
  • GHANEMGHANEM Dana, PhD
  • GOMPEL Marie, PhD
  • HUIN Vincent , MD, PhD
  • HUMEZ Sandrine, PhD
  • JUMEAU Fanny, PhD
  • LAMBERT Jean-Charles, PhD
  • LAURENT Cyril, PhD
  • LEBOUCHER Antoine, PhD
  • LECOLLE Katia, PhD
  • LEFRANC Didier, PhD
  • LE FRECHE Hélène, MD
  • LEGHAY Coline, PhD
  • LEROY Olivier, PhD
  • MAILLIOT Christel, PhD
  • MARCINIAK Élodie, PhD
  • MARINANGELI Claudia, PhD
  • MAURAGE Claude-Alain, MD, PhD
  • PAPEGAEY Anthony, PhD
  • PEREZ-TUR Jordi, PhD
  • PERMANNE Bruno, PhD
  • PODEVIN-DIMSTER Valérie, PhD
  • SAMBO Anne-Véronique, PhD
  • SAUTIERE Pierre-Éric, PhD
  • SCHINDOWSKI Katharina, PhD
  • SIGALA Julien, MD, PhD
  • SOULIE Cathia, PhD
  • SPOLCOVA Andrea, PhD
  • SULTAN Audrey, PhD
  • TARDIVEL-SAFI Meryem, PhD
  • TRAN Hélène, PhD
  • TROQUIER Lætitia, PhD
  • VERMERSCH Patrick, MD, PhD
  • VIOLET Marie, PhD
Our project has the following scheme: A. MAPT regulation: epigenomics, transcriptional and post-transcriptional B. New insights on Tau functions C. Modulating Tau pathology D. Translational research: diagnostic and therapeutic applications  

A. MAPT regulation: epigenomics, transcriptional and post-transcriptional

The human Tau / MAPT gene is unique and contains 16 exons located on more than 150 kb on the long arm of chromosome 17 (17q21). The Tau primary transcript contains 16 exons. In the human brain, exon -1 is transcribed but not translated. Exons 1, 4, 5, 7, 9, 11, 12, 13 and 14 are constituent exons. Exons 2, 3 and 10 are spliced ​​alternately and are specific to the adult brain. Thus, in the human brain, the alternative splicing of these three exons makes it possible to obtain six mRNAs (2-3-10-, 2 + 3-10-, 2 + 3 + 10-, 2-3-10 +; 2 + 3- 10+, 2 + 3 + 10 +) leading to the expression of 6 protein isoforms (3R (10-) and 4R (10+)). A growing body of literature suggests that change in alternative expression or splicing may contribute to Tau-related neurodegeneration. Thus, modification of the expression and / or splicing of MAPT leads to frontotemporal dementia but can also be observed in other Tauopathies including Alzheimer’s disease and myotonic dystrophy, CUG triplet expansion disease. It is therefore essential to understand the epigenomic, the transcriptional and post-transcriptional regulation of the MAPT gene.

B. New insights on Tau functions

Tau protein is originally defined as a microtubule-associated protein. Tau is also a signaling protein that clearly has other functions in the neuron and neuronal networks via membrane, nuclear and extracellular processes. These new functions can be carried by specific protein domains and / or post-translational modifications (phosphorylation, acetylation, proteolysis, etc.).

 In this context, the laboratory is interested in (1) the role of Tau in the nucleus in particular in the protection of nucleic acids, the structure of chromatin and transcription; (2) the role of new amino-truncated forms of Tau in neuronal signaling and physiopathological development, particularly in patients; (3) the role of Tau as an extracellular signaling factor with the aim of understanding the mechanisms leading to its secretion under physiological and pathological conditions; (4) the role of Tau as a regulator of neuronal signaling.

C. Modulating Tau pathology

The laboratory is interested rôle pathogénique des différentes espèces moléculaire in the pathogenic role of the different molecular species of Tau especially in the prion-like spreading hypothesis. We are also interested in the role of extrinsic factors in the toxicity of these species with an interest for APP and the Tau-Aß interface, the role of potential pathological modulators resulting from proteomic / transcriptomic / genomic analyzes (GWAS with LabEx DISTALZ ), environmental factors (including caffeine and its targets, A2A adenosinergic receptors) and cellular factors (neurons vs. glial cells).

D. Translational research: diagnostic and therapeutic applications

Our laboratory is committed to developing recherche translationnelle en interface avec les biologistes et clinicientranslational research in interface with biologists and clinicians. On one hand, we are interested in the identification of markers in autopsy-derived brain specimens and also body fluids (cerebrospinal fluid, blood…), allowing the differential diagnosis of dementia. We are developing a small cohort ECTAUSOME for a proof of concept. The emergence of new predictive biomarkers is essential for therapeutic implementation. On the other hand, we are developing preclinical research aimed at defining new therapeutic strategies. As such, we are exploring new anti-Tau compounds either by small molecule approaches (anti-aggregating, targeting protein chaperones…) in collaboration with the team of Patricia Melnyk – or immunotherapeutic approaches. The adenosinergic receptor pathway is also explored. These approaches are conducted in partnership with industry. It is notable that one of our molecules (MSBD) has led to the development of a company (AlzProtect) and a clinical trial. This molecule should move into phase 2 soon.

In conclusion, the strength of our laboratory welcoming researchers (biochemists, cell and molecular biologists, neurobiologists) and clinicians is to integrate fundamental, pre-clinical and clinical approaches to better understand the biology of Tau, its physiopathological role and the impact in terms of diagnosis and therapy.

• Publications
Patents
PhD Theses

Publications

2020

Ando K, De Decker R, Vergara C, Yilmaz Z, Mansour S, Suain V, Sleegers K, de Fisenne MA, Houben S, Potier MC, Duyckaerts C, Watanabe T, Buée L, Leroy K, Brion JP (2020) Picalm reduction exacerbates tau pathology in a murine tauopathy model. Acta Neuropathol, 139:773–789 doi:10.1007/s00401-020-02125-x

Boue-Grabot E, Blum D, Ceruti S. Editorial: Purinergic Signaling in Health and Disease. Front Cell Neurosci. 2020 Feb 4;14:15

Colin M, Dujardin S, Schraen-Maschke S, Meno-Tetang G, Duyckaerts C, Courade JP, Buée L (2020) Exploring anti-tau immunotherapy within the hypothesis of the prion-like propagation. Acta Neuropathol, 139: 3-25

Duriez P, Eddarkaoui S, Blum D, Gorwood P, Tolle V, Viltart O. Does physical activity associated with chronic food restriction alleviate anxiety like behaviour, in female mice? Horm Behav. 2020 Jun 13:104807

Hector A, McAnulty C, Piché-Lemieux ME, Alves-Pires C, Buée-Scherrer V, Buée L*, Brouillette J* (2020) Tau hyperphosphorylation induced by the anesthetic agent ketamine/xylazine involved the calmodulin-dependent protein kinase II. FASEB J, 34(2):2968–2977

Gomez-Murcia V, Sandau U, Ferry B, Parrot S, Laurent C, Basquin M,  Buée L, Boison D, Blum D (2020) Hyperexcitability and seizures in the THY-Tau22 mouse model of Tauopathy. Neurobiol Aging, 94:265-270.

Homa M, Loyens A, Eddarkaoui S, Faivre E, Deramecourt V, Maurage CA, Buée L, Huin V, Sablonnière B (2020) The TMEM240 Protein, Mutated in SCA21, Is Expressed in Purkinje Cells and Synaptic Terminals. Cerebellum 19(3):358‐369. doi:10.1007/s12311-020-01112-y

Montembeault M, Sayah S, Rinaldi D, et al. Cognitive inhibition impairments in presymptomatic C9orf72 carriers. J Neurol Neurosurg Psychiatry. 2020;91(4):366-372. doi:10.1136/jnnp-2019-322242

Nebie O, Barro L, Wu YW, Knutson F, Buée L, Devos D, Peng CW, Blum D, Burnouf T (2019) Heat-treated human platelet lysate modulates microglia activation, favors wound healing and promotes neuronal differentiation in vitro. Platelets, in press

Richetin K, Steullet P, Pachoud M, Perbet R, Parietti E, Maheswaran M, Eddarkaoui S, Bégard S, Pythoud C, Rey M, Caillierez R, Do KQ, Halliez S, Bezzi P, Buee L, Leuba G, Colin M, Toni N, Déglon N. Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer’s disease. Nature Neurosci, in press.

Sellami L, Rucheton B, Ben Younes I, et al. Plasma progranulin levels for frontotemporal dementia in clinical practice: a 10-year French experience. Neurobiol Aging. 2020;91:167.e1-167.e9.

Sierksma A, Lu A, Salta E, Mancuso R, Zoco J, Blum D, Buée L, De Strooper B, Fiers M (2020) Novel Alzheimer risk genes determine the microglia response to amyloid ß but not to TAU pathology. EMBO Mol Med, in press.

Temido-Ferreira M, Ferreira DG, Batalha VL, Marques-Morgado I, Coelho JE, Pereira P, Gomes R, Carvalho S, Canas PM, Cuvelier L, Buée-Scherrer V, Faivre E, CE, Pimentel J, Schiffmann SN, Buée L, Outeiro TF, Bader M, Blum D, Cunha RA, Marie H, Pousinha PA, Lopes LV (2020) Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors. Mol Psychiatr, in press.

Verelst J, Geukens N, Eddarkaoui S, Vliegen D, De Smidt E, Rosseels J, Franssens V, Molenberghs S, Francois C, Stoops E, Bjerke M, Engelborghs S, Laghmouchi M, Carmans S, Buée L, Vanmechelen E, Winderickx J, Thomas D (2020) A Novel Tau Antibody Detecting the First Amino-Terminal Insert Reveals Conformational Differences Among Tau Isoforms. Front Mol Biosci, 7:48. doi:10.3389/fmolb.2020.00048

Zheng J, Akbari M, Schirmer C, Reynaert ML, Loyens A, Lefebvre B, Buée L, Croteau DL, Galas MC, Bohr VA (2020) Hippocampal tau oligomerization early in tau pathology coincides with a transient alteration of mitochondrial homeostasis and DNA repair in a mouse model of tauopathy. Acta Neuropathol Commun, 8(1):25. doi:10.1186/s40478-020-00896-8

2019

Albert M, Mairet-Coello G, Danis C, Lieger S, Caillierez R, Carrier S, Skrobala E, Landrieu I, Michel A, Schmitt M, Citron M, Downey P, Courade JP, Buée L*, Colin M* (2019) Prevention of tau seeding and propagation by immunotherapy with a central tau epitope antibody. Brain, 142(6):1736-1750

Bernard C, Zappettini S, Faivre E, Ghestem A, Carrier S, Buee L, Blum D, Esclapez M (2019) Caffeine consumption during pregnancy accelerates the development of cognitive deficits in offspring in a model of tauopathy. Frontiers Cell Neurosci, 13: 438.

Blommaert D, Sergeant N, Delehedde M, et al. Expression, localization, and concentration of A-kinase anchor protein 4 (AKAP4) and its precursor (proAKAP4) in equine semen: Promising marker correlated to the total and progressive motility in thawed spermatozoa. Theriogenology. 2019;131:52-60.

Bossenmeyer-Pourié C, Smith AD, Lehmann S, et al. N-homocysteinylation of tau and MAP1 is increased in autopsy specimens of Alzheimer's disease and vascular dementia. J Pathol. 2019;248(3):291-303.

Carvalho K, Faivre E, Pietrowski MJ, Marques X, Gomez-Murcia V, Deleau A, Huin V, Hansen JN, Kozlov S, Danis C, Temido-Ferreira M, Coelho JE, Mériaux C, Eddarkaoui S, Le Gras S, Dumoulin M Cellai L, NeuroCEB Brain Bank, Landrieu I, Chern Y, Hamdane M, Buée L, Boutillier AL, Levi S, Halle A, Lopes LV, Blum D (2019) Exacerbation of C1q dysregulation, synaptic loss and memory deficits in Tau pathology linked to neuronal adenosine A2Areceptors. Brain, 142(11): 3636-54

Chaalal A, Poirier R, Blum D, Laroche S, Enderlin V. Thyroid Hormone Supplementation Restores Spatial Memory, Hippocampal Markers of Neuroinflammation, Plasticity-Related Signaling Molecules, and β-Amyloid Peptide Load in Hypothyroid Rats. Mol Neurobiol. 2019 Jan;56(1):722-735

Corvol JC, Buée L (2019) A new step towards targeting tau. Lancet Neurol, 18:517-8.

Domise M, Sauvé F, Didier S, Caillerez R, Bégard S, Carrier S, Colin M, Marinangeli C, Buee L, Vingtdeux V (2019) Neuronal AMP-activated protein kinase (AMPK) hyper-activation induces synaptic loss by an autophagy mediated process. Cell Death Dis, 10:221

Dupré E, Danis C, Arrial A, Cantrelle FX, Merzougui H, Hanoulle X, Colin M, Rain JC, Buée L*, Landrieu I* (2019) Single chain antibody fragments as new tools for studying the neuronal Tau protein physiopathology. ACS Chemical Neurosci, 10(9):3997-4006

Faldini E, Ahmed T, Buee L, Blum D, Balschun D (2019) Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models. Acta Neuropathol Comm, 7:202 

Fichou Y, Al-Hilaly YK, François Devred F, Smet-Nocca C Tsvetkov PO, Verelst J, Winderickx J, Geukens N, Vanmechelen E, Perrotin A, Serpell L, Hanseeuw B, Medina M, Buée L*, Landrieu I* (2019) The elusive Tau Molecular structures: Can we translate the recent breakthroughs into new targets for intervention? Acta Neuropathol Commun, 7:31

Gary C, Lam S, Herard AS, Koch JE, Petit F, Gipchtein P, Sawiak SJ, Caillierez R, Eddarkaoui S, Colin M, Aujard F, Deslys JP, French neuropathology network, Brouillet E, Buée L, Comoy EE, Pifferi F, Picq JL, Dhenain M (2019) Encephalopathy induced by Alzheimer brain inoculation in a non-human primate. Acta Neuropathol Commun, 7(1)126.

Houben S, Leroy K, Ando K, Yilmaz Z, Widomski C, Buée L, Brion JP (2019) Genetic ablation of tau in postnatal neurons rescues decreased adult hippocampal neurogenesis in a tauopathy model. Neurobiol Dis, 127:131-141  https://pubmed.ncbi.nlm.nih.gov/30818066/

Ising C, Venegas C, Zhang S, Scheiblich H, Schmidt SV, Vieira-Saecker A, Schwartz S, Albasset S, McManus R, Tejera D, Griep A, Santarelli F, Brosseron F, Opitz S, Stunden J, Merten M, Kayed R, Golenbock D, Blum D, Latz E, Buee L, Heneka M (2019) NLRP3 inflammasome activation drives tau pathology. Nature, 575(7784): 669-673

Jadhav S, Avila J, Schöll M, Kovacs G, Kövari E, Skrabana R, Evans L, Kontsekova E, Malawska B, de Silva R, Buée L*, Zilka N* (2019) A walk through tau therapeutic strategies. Acta Neuropathol Commun, 7: 22.

Leboucher A, Ahmed T, Caron E, Tailleux A, Raison S, Joly Amado A, Marciniak E, Carvalho K, Hamdane M, Bantubungi K, Lancel S, Eddarkaoui S, Caillierez R, Vallez E, Staels B, Vieau D, Balschun D, Buée L*, Blum D* (2019) Brain insulin response and peripheral metabolic changes in a Tau transgenic mouse model. Neurobiol Dis, 125 :14-22.

Lemaire Q, Raffo-Romero A, Arab T, Van Camp C, Drago F, Forte S, Gimeno JP, Begard S, Colin M, Vizioli J, Sautiere PE, Salzet M, Lefebvre C. Isolation of microglia-derived extracellular vesicles: towards miRNA signatures and neuroprotection. J Nanobiotechnology. 2019 Dec 4;17(1):119

Loera-Valencia R, Cedazo-Minguez A, Kenigsberg PA, Page G, Duarte A, Giusti P, Zusso M, Robert P, Frisoni G, Cattaneo A, Zille M, Boltze J, Cartier N, Buee L, Johansson G, Winblad B (2019) Current and emerging avenues for Alzheimer’s disease drug targets. J Intern Med, 286(4):398-437

Nebie O, Devos D, Vingtdeux V, Barro L, Devedjian JC, Jonneaux A, Chou ML, Bordet R, Buée L, Knutson F, Blum D, Burnouf T (2019) The neuroprotective activity of heat-treated human platelet lysate biomaterials manufactured from outdated pathogen-reduced (amotosalen/UVA) platelet concentrates. J Biomed Sci, 26(1):89. doi: 10.1186/s12929-019-0579-9

Nixon B, Bernstein IR, Cafe SL, Delehedde M, Sergeant N et al. A Kinase Anchor Protein 4 Is Vulnerable to Oxidative Adduction in Male Germ Cells. Front Cell Dev Biol. 2019;7:319.

Sergeant N, Vingtdeux V, Eddarkaoui S, Gay M, Le Fur N, Evrard C, Laurent C, Caillierez R, Obriot H, Larchanché PE, Farce A, Coevoet M, Carato P, Kouach M, Descat A, Dallemagne P, Buée-Scherrer V, Hamdane M, Buee L, Melnyk P (2019) New piperazine multi-effect drugs prevent neurofibrillary degeneration and amyloid deposition, and preserve memory in animal models of Alzheimer’s disease. Neurobiol Dis, 129: 217-33.

Shrivastava AN, Redeker V, Pieri L, Bousset L, Renner M, Madiona K, Mailhes-Hamon C, Coens A, Buée L, Hantraye P, Triller A, Melki R (2019) Clustering of tau fibrils impairs the synaptic composition of 3-Na+/K+-ATPase and AMPA receptors. EMBO J, 38, e99871

Wen J, Zhang H, Alexander DC, et al. Neurite density is reduced in the presymptomatic phase of C9orf72 disease. J Neurol Neurosurg Psychiatry. 2019;90(4):387-394.

2018

Benhelli-Mokrani H, Chauderlier A, Mansuroglu Z, Albaud B, Gentien D, Sommer S, Schirmer C, Laqueuvre L, Josse T, Buee L, Lefebvre B, Galas MC, Soues S, Bonnefoy E (2018) Genome-wide identification of neuronal DNA regions bound by Tau protein under physiological and stress conditions. Nucleic Acids Res, 46(21):11405-11422

Bergeron D, Gorno-Tempini ML, Rabinovici GD, et al. Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia. Ann Neurol. 2018;84(5):729-740.

Blum D, Chern Y, Domenici MR, Buee L, Lin CY, Rea W, Ferre S, Popoli P. The role of adenosine tone and adenosine receptors in Huntington’s disease. J Caffeine and Adenosine Res, 8: 43-58.

Cellai L, Carvalho K, Faivre E, Deleau A, Vieau D, Buée L, Blum D, Meriaux C, Gomez Murcia V (2018) The adenosinergic signaling: a complex but promising therapeutic target for Alzheimer’s disease. Frontiers Neurosci, 12: 520

Chatterjee S, Cassel R, Schneider-Anthony A, Merienne K, Cosquer B, Tzeplaeff L, Halder Sinha S, Kumar M, Chaturbedy P, Eswaramoorthy M, Le Gras S, Keime C, Bousiges O, Dutar P, Petsophonsakul P, Rampon C, Cassel JC, Buée L, Blum D, Kundu TK, Boutillier AL (2018) Reinstating plasticity and memory in a tauopathy mouse model with an acetyltransferase activator. EMBO Mol Med, 10(11). pii: e8587.

Chauderlier A, Gilles M, Spolcova A, Caillierez R, Chwastyniak M, Kress M, Drobecq H, Bonnefoy E, Pinet F, Weil D, Buee L, Galas MC, Lefebvre B (2018) Tau/DDX6 interaction increases microRNA activity. BBA Gene Regulatory Mechanisms, 8: 762-72.

d’Orange M, Aurégan G, Cheramy D, Gaudin-Guérif M, Lieger S, Guillermier M, Stimmer L, Joséphine C, Hérard AS, Gaillard MC, Petit F, Kiesslings MC, Schmitz C, Colin M, Buee L, Panayi F, Diguet E, Brouillet E, Hantraye P, Bemelmans AP, Cambon K (2018) Potentiating tangle formation reduces acute toxicity of soluble Tau species in the rat. Brain, 141(2):535-549.

Dujardin S, Lachaud C, Caillierez R, Bégard S, Carrier S, Lieger S, Gonzales JA, Moore BD, Deramecourt V, Deglon N, Maurage CA, Frosch MP, Hyman BT, Colin M, Buée L (2018)  Different Tau species lead to heterogeneous Tau pathology propagation and misfolding. Acta Neuropathol Commun, 6:132

Duron E, Vidal JS, Grousselle D, Gabelle A, Lehmann S, Buée L, Allinquant B, Schraen-Maschke S, Baret C, Rigaud AS, Hanon O, Epelbaum J (2018) Somatostatin and neuropeptide Y in cerebrospinal fluid: correlations with amyloid peptides Aß1-42, and tau proteins in elderly patients with mild cognitive impairment. Frontiers Aging Neurosci, 10 : 297.

Faivre E, Coelho JE, Zornbach K, Malik E, Schneider M, Cellai L, Carvalho K, Sebda S, Figeac M, Eddarkaoui S, Caillierez R, Chern Y, Heneka M, Sergeant N, Muller CE, Halle A, Buée L, Lopes LV, Blum D (2018) Beneficial effect of an adenosine A2AR antagonist in the APPswe/PS1dE9 mouse model of Alzheimer’s Disease. Frontiers Mol Neurosci, 11:235.n

Gay M, Evrard C, Descamps F, Carato P, Renault N, Coevoet M, Eddarkaoui S, Baud C, Larchanche PE, Buee L, El Bakali J, Vingtdeux V, Sergeant N, Melnyk P (2018) Biaryl-Based Amyloid Precursor Protein Modulators: Toward a New Profile of Indirect A Phenotypic Approach to the Discovery of Compounds that Promote Non-Amyloidogenic Processing of the Amyloid Precursor Protein: Toward a New Profile of Indirect β-Secretase Inhibitors. Eur J Med Chem, 159: 104-125.

Giralt A, de Pins B, Cifuentes-Díaz C, et al. PTK2B/Pyk2 overexpression improves a mouse model of Alzheimer's disease. Exp Neurol. 2018;307:62-73

Goiran T, Duplan E, Chami M, Bourgeois A, El Manaa W, Rouland L, Dunys J, Lauritzen I, You H, Stambolic V, Bif√©ri MG, Barkats M, Pimplikar SW, Sergeant N, Colin M, Morais VA, Pardossi-Piquard R, Checler F, Alves da Costa C. ß-Amyloid Precursor Protein Intracellular Domain Controls Mitochondrial Function by Modulating Phosphatase and Tensin Homolog-Induced Kinase 1 Transcription in Cells and in Alzheimer Mice Models. Biol Psychiatry. 2018 Mar 1;83(5):416-427

Gratuze M, Joly-Amado A, Vieau D, Buée L, Blum D (2018) Mutual relationship between Tau and central insulin signalling: consequences for AD and Tauopathies ? Neuroendocrinology, 107: 181-95

Hanon O, Vidal JS, Lehmann S, Bombois S, Allinquant B, Tréluyer JM, Gelé P, Delmaire C, Blanc F, Buée L, Touchon J, Hugon J, Vellas B, Galbrun E, Benetos A, Berrut G, Paillaud E, Wallon D, Castelnovo G, Volpe–Gillot L, Paccalin M, Robert PH, Godefroy O, Dantoine T, Camus V, Belmin J, Vandel P, Novella JL, Duron E, Rigaud AS, Schraen S*, Gabelle* on behalf of the BALTAZAR study group (2018) Plasma amyloid levels within the Alzheimer’s process and correlations with central biomarkers. Alzheimers & Dementia, 14:858-68

Jumeau F, Sigala J, Dossou-Gbete F, Frimat K, Barbotin AL, Buée L, Behal H, Sergeant N, Mitchell V (2018) A-kinase anchor protein 4 precursor (pro-AKAP4) in human sperm. Andrology, 6(6):854-859

Laurent C, Buée L, Blum D (2018) Tau and neuroinflammation: what impact for Alzheimer’s disease and Tauopathies. Biomed J, 41: 21-33

Lee CC, Chang CP, Lin CJ, Lai HL, Kao YH, Cheng HC, Chen HM, Liao YP, Faivre E, Buée L, Blum D, Fang JM, Chern Y (2018) Adenosine augmentation evoked by an ENT1 inhibitor improves memory impairment and neuronal plasticity in the APP/PS1 mouse model of Alzheimer’s disease. Mol Neurobiol, 55(12):8936-8952

Marinangeli C, Didier S, Ahmed T, Caillerez R, Domise M, Laloux C, Bégard S, Carrier S, Colin M, Marchetti P, Ghesquière B, Balschun D, Buée L, Kluza J, Vingtdeux V (2018) AMP-activated protein kinase is essential for the maintenance of energy levels during synaptic activation. iScience, 9: 1-13.

Popelova A, Prazienkova V, Neprasova B, Kasperova BJ, Hruba L, Holubova M, Zemenova J, Blum D, Zelezna B, Galas MC, Kunes J, Maletinska L. Novel Lipidized Analog of Prolactin-Releasing Peptide Improves Memory Impairment and Attenuates Hyperphosphorylation of Tau Protein in a Mouse Model of Tauopathy. J Alzheimers Dis. 2018;62(4):1725-1736

Roudil J, Deramecourt V, Dufournet B, et al. Influence of Lewy Pathology on Alzheimer's Disease Phenotype: A Retrospective Clinico-Pathological Study. J Alzheimers Dis. 2018;63(4):1317-1323

Sierksma A, Lu A, Salta E, Vanden Eynden E, Callaerts-Vegh Z, D'Hooge R, Blum D, Buee L, Fiers M, De Strooper B (2018) Deregulation of neuronal miRNAs induced by either amyloid-β or TAU pathology. Mol Neurogener, 13(1):54.

Vandenbussche C, Van der Hauwaert C, Dewaeles E, Franczak J, Hennino MF, Gnemmi V, Savary G, Tavernier Q, Nottet N, Paquet A, Perrais M, Blum D, Mari B, Pottier N, Glowacki F, Cauffiez C. Tacrolimus-induced nephrotoxicity in mice is associated with microRNA deregulation. Arch Toxicol. 2018 Apr;92(4):1539-1550

Vercruysse O, Paquet C, Gabelle A, Delbeuck X, Blanc F, Wallon D, Dumurgier J, Magnin E, Martinaud O, Jung B, Bousiges O, Lehmann S, Delaby C, Quillard-Murain M, Peoc'h K, Laplanche JL, Bouaziz-Amar E, Hannequin D, Sablonniere B, Buee L, Hugon J, Schraen S, Pasquier F, Bombois S (2018) Relevance of Follow-Up in Patients with Core Clinical Criteria for Alzheimer Disease and Normal CSF biomarkers. Curr Alz Res, 15: 691-700

2017

Dourlen P, Fernandez-Gomez F, Dupont C, Grenier-Boley B, Bellenguez C, Obriot H, Caillierez R, Sottejeau Y, Chapuis J, Bretteville A, Abdelfettah F, Delay C, Malmanche N, Soininen H, Hiltunen M, Galas MC, Amouyel P, Sergeant N, Buée L, Dermaut B, Lambert JC (2017) Functional screening of Alzheimer risk loci identifies PTK2B as an in vivo modulator and early marker of Tau pathology. Mol Psychiatr, 22(6):874-883. doi: 10.1038/mp.2016.59

Duroux R, Renault N, Cuelho JE, Agouridas L, Blum D, Lopes LV, Melnyk P, Yous S. Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A2 receptor. J Enzyme Inhib Med Chem. 2017 Dec;32(1):850-864

Gibier JB, Hemon B, Fanchon M, Gaudelot K, Pottier N, Ringot B, Van Seuningen I, Glowacki F, Cauffiez C, Blum D, Copin MC, Perrais M, Gnemmi V. Dual role of MUC1 mucin in kidney ischemia-reperfusion injury: Nephroprotector in early phase, but pro-fibrotic in late phase. Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1336-1349

Huin V, Buée L, Behal H, Labreuche J, Sablonnière B, Dhaenens CM (2017) Alternative promoter usage generates novel shorter MAPT mRNA transcripts in Alzheimer’s disease and progressive supranuclear palsy brains. Sci Rep, 7(1):12589. doi: 10.1038/s41598-017-12955-7

Jumeau F, Chalmel F, Fernandez-Gomez FJ, Carpentier C, Obriot H, Tardivel M, Caillet-Boudin ML, Rigot JM, Rives N, Buée L, Sergeant N, Mitchell V (2017) Defining the human sperm microtubulome: an integrated genomics approach. Biol Reprod, 96(1) 93-106. doi: 10.1095/biolreprod.116.143479

Laurent C, Dorothée G, Hunot S, Martin E, Monnet Y, Duchamp M, Duong Y, Légeron FP, Leboucher A, Burnouf S, Faivre E, Carvalho K, Caillierez R, Zommer N, Demeyer D, Jouy N, Sazdovitch V, Schraen-Maschke S, Delarasse C, Buée L*, Blum D* (2017) Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of Tauopathy. Brain, 140(Pt 1):184-200. doi: 10.1093/brain/aww270

Lebouvier T, Pasquier F, Buée L (2017) Update on Tauopathies. Curr Op Neurol, 30(6):589-598

Marciniak E, Leboucher A, Caron E, Ahmed T, Tailleux A, Dumont J, Issad T, Gerhardt E, Pagesy P, Vileno M, Bournonville C, Hamdane M, Bantubungi K, Lancel S, Demeyer D, Eddarkaoui S, Vallez E, Vieau D, Humez S, Faivre E, Grenier-Boley B, Outeiro TF, Staels B, Amouyel P, Balschun D, Buee L*, Blum D* (2017) Tau deletion promotes brain insulin resistance. J Exp Med, 214(8):2257-2269. doi: 10.1084/jem.20161731

Moulin S, Leys D, Schraen-Maschke S, Bombois S, Mendyk AM, Muhr-Tailleux A, Cordonnier C, Buee L, Pasquier F, Bordet R (2017) Aβ1-40 and Aβ1-42 plasmatic levels in Stroke: Influence of pre-existing cognitive status and stroke characteristics. Curr Alzheimer Res 14(6): 686-694

Mudher A, Brion JP, Avila J, Medina M, Buée L (2017) EuroTau meeting: Towing scientists to Tau without tautology. Acta Neuropathol Commun, 5: 90

Mudher A, Colin M, Dujardin S, Medina M, Dewachter I, Alvavi Naini SM, Mandelkow EM, Mandelkow E, Buée L, Goedert M, Brion JP (2017) What is the evidence that Tau pathology spreads through a prion-like propagation ? Acta Neuropathol Comm, 5: 99

Paban V, Loriod B, Villard C, Buée L, Blum D, Pietropaolo S, Cho YH, Gory-Faure S, Mansour E, Gharbi A, Alescio-Lautier B (2017) Omics analysis of mouse brain models of human diseases. Gene, 600:90-100. doi: 10.1016/j.gene.2016.11.022

Shelkovnikova TA, Dimasi P, Kukharsky M, An H, Quintiero A, Schirmer C, Buée L, Galas MC, Buchman VL (2017) Chronically stressed or stress-preconditioned neurons fail to maintain stress granule assembly. Cell Death Dis, 8(5):e2788. doi: 10.1038/cddis.2017.199

Šimić G, Leko MB, Wray S, Harrington C, Delalle I, Jovanov-Milošević N, Bažadona D, Buée L, Silva R, Giovanni GD, Wischik C, Hof PR (2017) Monoaminergic Neuropathology in Alzheimer's disease. Prog Neurobiol, 151 : 101-138

Sotiropoulos I, Galas MC, Silva JM, Skoulakis E, Wegmann S, Maina MB, Blum D, Sayas CL, Mandelkow EM, Mandelkow E, Spillantini MG, Sousa N, Avila J, Medina M, Mudher A, Buee L (2017) Atypical, non-standard functions of the microtubule-associated Tau protein. Acta Neuropathol Comm, 5: 91

Vanden Dries V, Stygelbout V, Pierrot N, Yilmaz Z, Suain V, De Decker R, Buée L, Octave JN, Brion JP, Leroy K (2017) Amyloid precursor protein reduction enhances the formation of neurofibrillary tangles in a mutant tau transgenic mouse model. Neurobiol Aging, 55:202-212

Patents

Patented

  • EP17210486.1 Cauffiez C, Perrais M, Blum D. KIT-OF-PARTS COMPRISING A NEPHROTOXIC CHEMOTHERAPEUTIC DRUG AND A SELECTIVE A2A ADENOSINE RECEPTOR ANTAGONIST. December 22, 2017.
  • EP17305355.4 Hamdane M, Derisbourg M, Leghay C, Chiappetta G, Verdier Y, Vinh J, Blum D, Buée L. New Tau species. March 28, 2017.

Patents accepted

  • WO2015068075  –  Buée L, Colin M, Hantraye P, Aron Badin R, Dujardin S, Bemelmans A, Brouillet E. DETECTION OF TAU.
  • WO2014096321 – Buée L, Troquier L, Lassalle P. ANTIBODIES SPECIFIC TO TAU PHOSPHORYLATED AT SERINE 422 AND USES FOR THE TREATMENT AND DIAGNOSIS OF TAUOPATHIES.

Licenced Patents

  • US20160356785 Sergeant N, Mitchell V, Jumeau F, Sigala J. Methods for determining human sperm quality. Licence exclusive à 4BioDx.
  • WO2016146655 : Sergeant N, Melnyk P, Buée L. Novel 1,4-bis(3-aminopropyl)piperazine derivatives and its use. 16 mars 2015 (Accord de licence en discussion avec la société Alzprotect).
  • WO2015032842 : Sergeant N, Mitchell V, Jumeau F, Sigala J. Méthodes de détermination de la qualité du sperme humain. Licence exclusive à 4BioDx.
  • WO2014102339 : Barrier M, Buée L, Burlet S, Delacourte A, Estrella C, Melnyk P, Sergeant N, Verwaerde P. Sulfate salts of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine. AlzProtecT – phase I terminée en 2015.
  • W02006051489 : Melnyk Patricia, Sergeant Nicolas, Buée Luc, Delacourte André, Inserm, Université de Lille II, « Use of 1, 4-bis(3 aminopropyl)piperazine derivatives in therapy ». http://www.wipo.int/pctdb/en/wo.jsp?WO=2006051489 Licensed to AlzProtecT.
    Molécule actuellement en essai clinique chez l’homme – phase I terminée en 2015.

Phd Theses

Ongoing Phd

  • CARVALHO Kevin (D2 en 2017 – thesis director : David BLUM)
  • DENECHAUD Marine (D1 en 2018 – thesis director : Marie-Christine GALAS)
  • ERDUAL Edmone (D3 en 2017 – thesis director : Christelle CAUFFIEZ et David BLUM)
  • GUEDJDAL Sarah (D1 en 2017 – thesis director : Malika HAMDANE)
  • GUIRAUD Sebastien (D3 en 2018 – thesis director : MC GALAS/R PARDOSSI)
  • HOMA Megane (D2 en 2017 – thesis director : Bernard SABLONNIERE)
  • NEBIE Ouada (D1 en 2017 – thesis director : David BLUM et Thierry BURNOUF)
  • LEROUX Elodie (D1 en 2018 – thesis director : Morvane COLIN)
  • LEROY Melanie (D1 en 2018 – thesis director : Vincent DERAMECOURT)
  • PERBET Romain (D1 en 2017 – thesis director : Morvane COLIN)
  • RICO Thomas (D1 en 2018 – thesis director : Bruno LEFEBVRE)
  • SOUSA Cristiano (D1 en 2018 – thesis director : Malika HAMDANE et Karen VANHOORELBEKE)
  • TAUTOU Marie (D1 en 2018 – thesis director : Nicolas SERGEANT)
  • ZEJNELI Orgeta (D1 en 2018 – thesis director : Luc BUEE et Isabelle LANDRIEU)

Theses defended since 2013

  • ALBERT Marie (sout. le 10/12/2018 directed by Morvane COLIN) (title/abstract)
  • DANIS Clément (soutenance le 14/12/2018 directed by Isabelle LANDRIEU et Luc BUEE) (title/abstract)
  • DOMISE Manon (soutenance le 17/12/2018 directed by Valerie VINGTDEUX) (title/abstract)
  • EVRARD Caroline (sout. le 20/11/2018 directed by Nicolas SERGEANT) (title/abstract)
  • GILLES Melissa (sout. le 13/11/2018 directed by Bruno LEFEBVRE) (title/abstract)
  • TARDIVEL-SAFI Meryem (sout. le 6/12/2017 directed by Morvane COLIN) (title/abstract)
  • LEGHAY Coline (sout. le 19/09/2017 directed by Malika HAMDANE (title/abstract)
  • PAPEGAEY Anthony (sout. le 19/12/2016) directed by Valerie BUEE-SCHERRER (title/abstract)
  • CHAUDERLIER Alban (sout. le 16/12/2016) directed by Marie-Christine GALAS (title/abstract)
  • HUIN Vincent (sout. le 15/12/2016) directed by Bernard SABLONNIERE et Claire-Marie DHAENENS (title/abstract)
  • SIGALA Julien (sout. le 08/12/2016) directed by Valérie MITCHELL et Nicolas SERGEANT (title/abstract)
  • MARCINIAK Elodie (sout. le 14/12/2015) directed by Sandrine HUMEZ (title/abstract)
  • ALVES-PIRES Claire (sout. le 10/12/2015) directed by Luc BUEE et Christelle MONACA-CHARLEY (title/abstract)
  • SPOLCOVA Andrea (sout. le 23/09/2015) directed by Marie-Christine GALAS (title/abstract)
  • DUJARDIN Simon (sout. le 21/09/2015) directed by Morvane COLIN (title/abstract)
  • DERISBOURG Maxime (sout. le 30/03/2015) directed by Malika HAMDANE (title/abstract)
  • VIOLET Marie (sout. le 28/02/2014) directed by Marie-Christine GALAS (title/abstract)
  • LAURENT Cyril (sout. le 17/12/2013) directed by David BLUM (title/abstract)
  • CARPENTIER Céline (sout. le 16/12/2013)directed by Marie-Laure CAILLET-BOUDIN (title/abstract)
  • WATTEZ Jean-sébastien (sout. le 09/12/2013) directed by Didier VIEAU et Benoit FOLIGNE (title/abstract)
  • JUMEAU Fanny (sout. le 16/09/2013) directed by Valérie MITCHELL et Nicolas SERGEANT (title/abstract)