Team “Alzheimer’s disease and prion diseases ”

Scientific Teams

Presentation

Main domain: Cellular & molecular neuroscience Subdomain : Clinical & translational neurosciences The team has a strong background in Alzheimer’s disease andprions diseases and brings together researchers specializedon both diseases with the complementary skills and strategiesto foster emerging approaches and study common mechanisms. It notably relies on the central role of the investigators in brain banking (Neuro-CEB) and national centers of reference for prion diseases, and on the transversal knowledge from neuropathology to animal and cellular models both in Alzheimer and in prion’s fields.

The scientific objectives of the team have been to study (i) mechanisms of misfolded proteins production and toxicity associated to Aß and prion pathologies with a specific focus on the role of lipids,particularly cholesterol and ApoE in AD; (ii) amyloid and tau pathologies interplay; (iii) seeding and spreading of prion and Alzheimer’s pathologies including the characterization and understanding of of the strain phenomenon and (iv) to develop innovative approaches for the diagnosis and treatment of both diseases.
To reach these goals the team set up transversal approaches combining complementary expertise and technology including (i) cellular models of prion propagation and Aß production and spreading; (ii) protein misfolding amplification technologies; (iii)
mouse and C. elegans models of misfolded proteins propagation and toxicity at the functional and neuropathological levels with a special focus on early events; (iv) clinical, genetic and postmortem studies in patients for translating the team’s results to diagnosis and treatments in Alzheimer and prion’s diseases.
The involvement of the team in innovative approaches and translational research is exemplified by (i) numerous collaborations with industrials and biotechs; (ii) patents on technologies and treatments, one of them awarded by the CNRS Cristal Medal; (iii) transfer of technology through licensing of patent to the industry (SATT Lutech Trophées 2017).

Major publications

Brandel JP, Bustuchina-Vlaicu M, Culeux A, Belondrade M, Bougard D, Grznarova K, Denouel, A, Plu I, Bouaziz-Amar E, Seilhean D, Levasseur M & Haïk S. Variant Creutzfeldt-Jakob Disease Diagnosed 7.5 Years after Occupational Exposure. N Engl J Med. 2020 Jul 2;383(1):83-85.
Thierry M, Boluda S, Delatour B, Marty S, Seilhean D; Brainbank NeuroCEB Neuropathology Network, Potier MC, Duyckaerts C. Human subiculo-fornico-mamillary system in Alzheimer’s disease: Tau seeding by the pillar of the fornix. Acta Neuropathol. 2020 Mar;139(3):443-461.
Xicota L, Ichou F, Lejeune FX, Colsch B, Tenenhaus A, Leroy I, Fontaine G, Lhomme M, Bertin H, Habert MO, Epelbaum S, Dubois B, Mochel F, Potier MC; INSIGHT study group. Multi-omics signature of brain amyloid deposition in asymptomatic individuals at-risk for Alzheimer’s disease: The INSIGHT-preAD study. EBioMedicine. 2019 Sep;47:518-528.
Androuin A., Potier B., Nägerl U.V., Cattaert D., Danglot L., Thierry M., Youssef I., Triller A., Duyckaerts C., El Hachimi K.H., Dutar P., Delatour B., Marty S. Evidence for altered dendritic spine compartmentalization in Alzheimer’s disease and functional effects in a mouse model. Acta Neuropathol. 2018 Jun;135(6):839-854.
Haik S., Marcon G., Mallet A., Tettamanti M., Welaratne A., Giaccone G., Azimi S., Pietrini V., Fabreguettes J.R., Imperiale D., Cesaro P., Buffa C., Aucan C., Lucca U., Peckeu L., Suardi S., Tranchant, C., Zerr, I., Houillier, C., Redaelli, V., Vespignani, H., Campanella A., Sellal, F., Krasnianski, A., Seilhean, D., Heinemann, U., Sedel, F., Canovi, M., Gobbi, M., Di Fede G., Laplanche J.L., Pocchiari M., Salmona M., Forloni G., Brandel J.P. & Tagliavini F. (2014) Doxycycline in Creutzfeldt- Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 13, 150- 158.