Alzheimer’s disease, prion diseases

The 5 main objectives are:

• To study the interactions between cholesterol and APP peptide to modulate the production of amyloid aggregates.
• Characterize subcellular compartments where protein production is initiated.
• To study the role of the cerebral lymphatic system in the drainage of pathological proteins.
• To determine if specific proteins can be observed in patients with a different clinical profile.
• To study the mechanisms involved in the specific targeting of certain brain structures.

Alzheimer’s disease is a neurodegenerative disease that causes a progressive decline in cognition and memory. It is characterized by the appearance of lesions that gradually invade the brain and destroy neurons. Within the lesions, there is the excessive production and accumulation of amyloid-beta proteins that form plaques, called amyloid plaques or senile plaques, and the accumulation of modified proteins (Hyperphosphorylated Tau) that form neurofibrillary degeneracies that destroy neurons. These malfunctions result in disorganization of neural networks, leading to cognitive decline and then dementia. Prion diseases are rare diseases, characterized by degeneration of the central nervous system and the formation of aggregates of a specific misordered protein that accumulates, the prion protein. The most common is Creutzfeldt-Jakob Disease (CJD).

Main publications

• Cossec, J.C., Lavaur, J., Berman, D.E., Rivals, I., Hoischen, A., Stora, S., Ripoll, C., Mircher, C., Grattau, Y., Olivomarin, J.C., de Chaumont, F., Lecourtois, M., Antonarakis, S.E., Veltman, J.A., Delabar, J.M., Duyckaerts, C., Di Paolo, G. & Potier, M.C. (2012) Trisomy for synaptojanin1 in Down syndrome is functionally linked to the enlargement of early endosomes. Hum Mol Genet, 21, 3156-3172. (IF=6)
• Peoc’h, K., Levavasseur, E., Delmont, E., De Simone, A., Laffont-Proust, I., Privat, N., Chebaro, Y., Chapuis, C., Bedoucha, P., Brandel, J.P., Laquerriere, A., Kemeny, J.L., Hauw, J.J., Borg, M., Rezaei, H., Derreumaux, P., Laplanche, J.L. & Haik, S. (2012) Substitutions at residue 211 in the prion protein drive a switch between CJD and GSS syndrome, a new mechanism governing inherited neurodegenerative disorders. Hum Mol Genet, 21, 5417-5428. (IF=6)
• 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. (IF=27.1)
• Duyckaerts C, Sazdovitch V, Ando K, Seilhean D, Privat N, Yilmaz Z, Peckeu L, Amar E, Comoy E, Maceski A, Lehmann S, Brion JP, Brandel JP, Haïk S. Neuropathology of iatrogenic Creutzfeldt-Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathyand long incubation periods for the transmission of Abeta pathology. Acta Neuropathol. 2018 Feb;135(2):201-212. (IF=15.9)
• Androuin A, Potier B, Nägerl UV, Cattaert D, Danglot L, Thierry M, Youssef I, Triller A, Duyckaerts C, El Hachimi KH, 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. (IF=15.9)