Alzheimer’s and Prion Diseases

Leader

Co-Leaders

Research center

47 bld de l'Hôpital
75651 Paris
Alexis Brice

Institution

Inserm
CNRS
Université Pierre et Marie Curie
ED158
Université Pierre et Marie Curie

Laboratory

Phone: 01 42 16 18 81
UMRS 1127 UMR 7225
IHU-A-ICM

Keywords

Alzheimer’s disease
prion disease
Down syndrome
nauropathology
animal models
Available to host a PhD student

Publications

Hannaoui S, Gougerot A, Privat N, Levavasseur E, Bizat N, Hauw JJ, Brandel JP, Haïk S. Cycline efficacy on the propagation of human prions in primary cultured neurons is strain-specific. J Infect Dis. 2014 Apr 1;209(7):1144-8. doi: 10.1093/infdis/jit623. Epub 2013 Nov 21.

Pietri M, Dakowski C, Hannaoui S, Alleaume-Butaux A, Hernandez-Rapp J, Ragagnin A, Mouillet-Richard S, Haik S, Bailly Y,Peyrin JM, Launay JM, Kellermann O, Schneider B. PDK1 decreases TACE-mediated ?-secretase activity and promotes disease progression in prion and Alzheimer's diseases. Nat Med. 2013 Sep;19(9):1124-31.

Hannaoui S, Maatouk L, Privat N, Levavasseur E, Faucheux BA, Haïk S. Prion propagation and toxicity occur in vitro with two-phase kinetics specific to strain and neuronal type. J Virol. 2013 Mar;87(5):2535-48. doi: 10.1128/JVI.03082-12. Epub 2012 Dec 19.

Peoc'h K, Levavasseur E, Delmont E, De Simone A, Laffont-Proust I, Privat N,Chebaro Y, Chapuis C, Bedoucha P, Brandel JP,Laquerriere A, Kemeny JL, Hauw JJ, Borg M, Rezaei H, Derreumaux P, Laplanche JL, Haïk S. 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. 2012 Dec 15;21(26):5417-28.

Cossec JC, Lavaur J, Berman DE, Rivals I, Hoischen A, Stora S, Ripoll C, Mircher C, Grattau Y, Olivomarin JC, de Chaumont F, Lecourtois M, Antonarakis SE, Veltman JA, Delabar JM, Duyckaerts C, Di Paolo G, Potier MC. (2012) Trisomy for Synaptojanin1 in Down syndrome is functionally linked to the enlargement of early endosomes. Hum Mol Genet. Apr 17. [Epub ahead of print]

Tlili A, Hoischen A, Ripoll C, Benabou E, Badel A, Ronan A, Touraine R, Grattau Y, Stora S, van Bon B, de Vries B, Menten B, Bockaert N, Gecz J, Antonarakis SE, Campion D, Potier MC, Bléhaut H, Delabar JM, Janel N. (2012) BDNF and DYRK1A Are Variable and Inversely Correlated in Lymphoblastoid Cell Lines from Down Syndrome Patients. Mol Neurobiol. Jun 5.

Fields of research

Neurological and psychiatric diseases

Research Theme

We have interest in dementia characterized by the accumulation of amyloid proteins and neurodegeneration.
Modulation of A-beta secretion by cholesterol may have therapeutic implications. We are studying the lipid content of senile plaques using mass spectrometry. We investigate changes in A-beta secretion, APP endocytosis/trafficking and endosome morphology following cholesterol changes. We use Down syndrome models for the search of early markers of Alzheimer disease. We have identified early markers of neuronal dysfunction in transgenic animals. We inject oligomers of A-beta in mouse brains to study early events of neurodegeneration.

Prions exist as multiple strains that differentiate by the patterns of neurodegeneration they produce. Molecular basis of human strain diversity and properties remains enigmatic and, beyond the prion field, may be relevant to other proteinopathies. They are studied by taking advantage of our expertise in human prion disorders and models recently set up in the team including primary neurons and genetic models in C.Elegans. Search for anti-prion molecules and studies on the relationship between PrP, tau and A-beta are in progress.



Team members

BEAUDRY Patrice
BIZAT Nicolas
BRANDEL
DELATOUR
DAUPHINOT
PRIVAT
DUYCKAERTS Charles