1998 - ARTICLES PUBLIÉS DANS DES OUVRAGES

1998-11 Buee L, Hof P, Delacourte A. Alzheimer's disease vasculopathy. Stroke and Alzheimer's disease edited by D. Leys, F. Pasquier, P. Scheltens. Current issues in neurodegenerative diseases volume 9 editors E.C Wolters, P. Scheltens. Hollan academic graphics. The Hague. The Netherlands. 101-111.

1998-12 Delacourte A, Sergeant N, Wattez A, Robitaille Y. The biochemistry of the cytoskeleton in Pick complex. Pick’s disease and Pick complex, edited by A. Kertesz and D.G. Munoz, John Wiley & Sons, Inc. 243-258.

1998-13 Delacourte A. Le diagnostic moléculaire de la maladie d'Alzheimer sporadique: théories, faits et réalités. Actualités sur la maldie d'Alzheimer et les syndromes apparentés. Sous la direction de M.C Gely-Nargeot, K Ritchie, J. Touchon. Edité par Solal. 1998;43-47.

1998-14 Dupont-Wallois L, Delacourte A. Caillet-Boudin Ml. Etude de la phosphorylation des protéines Tau après transfection des cellules de neuroblastome humain par l'ADN c de l'isoforme la plus longue. Actualités sur la maladie d'Alzheimer et les syndromes apparentés. Sous la direction de M.C Gely-Nargeot, K Ritchie, J. Touchon. Edité par Solal. 1998;49-56.

1998-15 Sergeant N, Lefranc D, Buee L, David J-P, Vermersch P, Wattez A, Delacourte A. Characterization of PHF-Tau in Alzheimer's disease. Research and Practise in Gerontology, 1998, 101-114.

1998 - PUBLICATIONS DANS DES REVUES NATIONALES
1998-16 DELACOURTE A. Les diagnostics de la maladie d’Alzheimer. Annales de Biologie Clinique. 1998, 56:133-142

Neurosci Lett 1998 Jul 3;250(2):83-86

Apolipoprotein E and Tau phosphorylation in human neuroblastoma cells.

Caillet-Boudin ML, Dupont-Wallois L, Soulie C, Delacourte A

INSERM U422, Pl. Verdun, Lille, France. caillet@.biserte.inserm.lille.fr

Phosphorylation is the major post-translational modification of Tau proteins and it plays an important role in Tau biological functions. Hyperphosphorylation of these proteins occurs during neurodegenerative disorders such as Alzheimer's disease. It was hypothesized that some variants of apolipoprotein E (apo E) may have a protective effect against the normal or pathological phosphorylation of Tau proteins. We have recently shown that apo E synthesis occurs in human SY 5Y and Kelly neuroblastoma cell lines which express different isoforms (E3 for SY 5Y; E3 and E4 for Kelly) [Dupont-Wallois, L., Soulie, C., Sergeant, N., Wavrant-de Wrieze, F., Chartier-Harlin, M.C., Delacourte, A. and Caillet-Boudin, M.L., Neurobiol. Dis., 4 (1997) 356-364]. Therefore, this cellular model makes it possible to study the differential influence, if any, of apo E3 and E4 on Tau phosphorylation. Using a large panel of Tau phosphorylation-dependent antibodies, we were not able to detect a significant difference in Tau immunoreactivity linked to the different apo E genotypes, even when the hyperphosphorylation of Tau proteins was induced by treating cells with Okadaic acid (OA), an inhibitor of phosphatase 1 and 2A proteins. Thus, a difference in apo E isoforms had no dramatic effect upon Tau phosphorylation in native or OA treated cells.

Vulnerable neuronal subsets in Alzheimer's and Pick's disease are distinguished by their tau isoform distribution and phosphorylation.

Delacourte A, Sergeant N, Wattez A, Gauvreau D, Robitaille Y

Unite INSERM 422, Lille, France.

Aggregated tau proteins constitute the basic matrix of neuronal inclusions specific to numerous neurodegenerative disorders. Monodimensional and two-dimensional Western blot analyses performed on cortical brain homogenates allowed discrimination between disease-specific tau protein profiles. These observations raised the issue of the physiopathological significance of such specificities. Alzheimer's disease (AD) pathological tau proteins (PTPs) (tau 74, 69, 64, 55) were compared with those of Pick's disease (PiD) (tau 64, 55) using a panel of antibodies against peptidic sequences of tau isoforms corresponding to exons 2, 3, and 10. AD and PiD could then be critically differentiated by the absence of translated tau isoforms with exon 10 in PiD PTPs, along with the absence of the phosphorylation site on Ser262. Immunohistochemical studies corroborate these findings. Indeed, Pick bodies were strongly immunostained by an anti-"exon 2" antibody but failed to reveal any anti-exon 10 reactive epitope. Tangles in AD contained exon 2, 3, and 10 epitopes. Altogether, our results demonstrated that Pick bodies develop within specific neuronal subsets that express specific patterns of 7 isoforms lacking exon 10 peptidic sequence. We conclude that neurodegenerative disorders imply attrition of selectively vulnerable neuronal subsets, a process revealed, and may be sustained by specific tau isoform patterns.

Lambert JC, Berr C, Pasquier F, Delacourte A, Frigard B, Cottel D, Perez-Tur J, Mouroux V, Mohr M, Cecyre D, Galasko D, Lendon C, Poirier J, Hardy J, Mann D, Amouyel P, Chartier-Harlin MC

INSERM CJF95-05, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille Cedex, France, INSERM U360, Hopital de la Salpetriere, 75651 Paris Cedex 13, France, CHR et U de Lille, Clinique Neurologique, Centre de la Me.

Possession of the apolipoprotein E ( APOE ) straightepsilon4 allele is the most frequently associated genetic susceptibility factor for Alzheimer's disease (AD). Recently, new polymorphisms in the regulatory region of the APOE gene have been described. We analysed the effects of three of these mutations (-491 AT, -427 CT and Th1/E47cs) on disease risk in a large case-control study, and tested their impacts on APOE allelic expression in brain tissues. The Th1/E47cs T allele was associated with an increased risk of occurrence of AD, while the -491 T allele was associated with a decreased risk, independently of the APOE straightepsilon2/straightepsilon3/straightepsilon4 polymorphism effect. However, the impact of the Th1/E47cs mutation was the strongest. The -427 CT polymorphism was not associated with the disease. In AD subjects heterozygous for the straightepsilon4 allele, analysis of allelic expression showed that the relative expression levels of the straightepsilon4 allele were higher than those of the corresponding controls. Consistent with epidemiological data, the relative level of expression of the straightepsilon4 allele was modified accordingly to the presence or absence of the two main promoter polymorphisms, indicating, in vivo , the deleterious effect of the Th1/E47cs T allele and the protective effect of the -491 T allele in population. These data indicate that in addition to the qualitative effect of the APOE straightepsilon2/straightepsilon3/straightepsilon4 polymorphisms on the AD occurrence, the quantitative variation of expression of these alleles due to functional APOE promoter mutations, is a key determinant of AD development.

1. PUBLICATION DANS DES OUVRAGES
2. Buée L, Hof P, Delacourte A. Alzheimer's disease vasculopathy. Stroke and Alzheimer's disease edited by D. Leys, F. Pasquier, P. Scheltens. Current issues in neuordgenerative diseases volume 9 editors E.C Wolters, P. Scheltens. Hollan academic graphics. The Hagure. The Netherlands. 101-111.
3. Delacourte A, Sergeant N, Wattez A, Robitaille Y. The biochemistry of the cytoskeleton in Pick complex. PickÕs disease and Pick complex, edited by A. Kertesz and D.G. Munoz, John Wiley & Sons, Inc. 243-258.
4. Delacourte A.Le diagnostic moléculaire de la maladie d'Alzheimer sporadique: théories, faits et réalités. Actualités sur la maldie d'Alzheimer et les syndromes apparentés. Sous la direction de M.C Gely-Nargeot, K Ritchie, J. Touchon. Edité par Solal. 1998;43-47.
5. Dupont-Wallois L, Delacourte A. Caillet-Boudin ML. Etude de la phosphorylation des protéines Tau après transfection des cellules de neuroblastome humain par l'ADN c de l'isoforme la plus longue. Actualités sur la maldie d'Alzheimer et les syndromes apparentés. Sous la direction de M.C Gely-Nargeot, K Ritchie, J. Touchon. Edité par Solal. 1998;49-56.
6. Sergeant N, Lefranc D, Buée L, David J-P, Vermersch P, Wattez A, Delacourte A. Characterization of PHF-Tau in Alzheimer's disease. Research and Practise in Gerontology, 1998, 101-114.
7. Wattez A, Robitaille Y. The biochemistry of the cytoskeleton in Pick complex. PickÕs disease and Pick complex, edited by A. Kertesz and D.G. Munoz, John Wiley & Sons, Inc. 243-258.

   1998 - publications dans des revues nationales

8. Delacourte A. Les diagnostics de la maladie d'Alzheimer. Annales de Biologie Clinique. 1998, 56:133-142

9. ABSTRACTS, POSTERS

10. BUEE L., BUSSIERE T., MAILLIOT C., SERGEANT N., WATTEZ A., DELACOURTE A. Les isoformes de protéines tau sont des marqueurs de sous-populations neuronales vulnérables dans les maladies neurodégénératives. Journées de neurologie de langue française, 1-4 avril 1998, Paris. Rev. Neurol., 154: 1S36.
11. BUEE L., MAILLIOT C., BUSSIERE T., SERGEANT N., WATTEZ A., DELACOURTE A. Both sets of tau isoforms and their hyperphosphorylation explain the different biochemical signatures observed in neurodegenerative processes. Sixth International Conference on Alzheimer's disease and related disorders, Amsterdam, 18-23 Juillet 1998.
12. BUSSIERE T., SERGEANT N., BUEE L., DELACOURTE A. The biochemical pathway of neurofobrillary degeneration in aging and Alzheimer's disease; Sixth International Conference on Alzheimer's disease and related disorders, Amsterdam, 18-23 Juillet 1998.
13. BUSSIERE T., HOF P.R., MAILLIOT C., BROWN C.D., PERL D.P., BUEE L., DELACOURTE A.Phosphorylated serine 422 on tau proteins is a pathologic epitope found in several diseases with neurofibrillary degeneration. 2ème journée de LARC - Neurosciences. Univ. Caen, 2 octobre 1998.
14. BUSSIERE T., DAVID J.P., BUEE L., WATTEZ A., SERGEANT N., PASQUIER F., LEBERT F., PETIT H., DIMENZA C., DELACOURTE A. Criteria to Establish a Biochemical (postmortem) Diagnosis of AlzheimerÕs Disease (CEBDAD). Lille Neurological Workshop, Lille, 27-28 novembre 1998. Rev. Neurol, 1998, 3S13
15. Caillet-Boudin M.L, Dupont-Wallois L., Soulié C., Delacourte A. Etablissement d'un modèle cellulaire de dégénérescence neuronale de type Alzheimer. Journées de neurologie de langue française. Paris-la Villette. 1-4 Avril 1998.
16. Caillet-Boudin M.L., Dupont-Wallois L., Soulié C., Sergeant, N. Delacourte A. Alzheimer-type phosphorylation of Tau proteins in human neuroblastoma cellss transfected by the longuest Tau isoform. 6th international conference on Alzheimer's disease. Amsterdam. 18-23 July 98.
17. DELACOURTE A., DAVID J.P., SERGEANT N., BUEE L., WATTEZ A., PASQUIER F., LEBERT F., GHOZALI F., FALLET-BIANCO C., DIMENZA C. Description moléculaire de la progression de la dégénérescence neurofibrillaire au cours du vieillissement cérébral et de la maladie dÕAlzheimer. Journées de neurologie de langue française, 1-4 avril 1998, Paris. Rev Neurol, 154: 1S37.
18. DELACOURTE A., DAVID J.P., BUEE L., WATTEZ A., SERGEANT N., VERMERCH P., GHOZALI F., FALLET-BIANCO C., PASQUIER F., LEBERT F., PETIT H., DIMENZA C. CEBDAD: Criteria to establish a biochemical (postmortem) diagnosis of Alzheimer's disease. Sixth International Conference on Alzheimer's disease and related disorders, Amsterdam, 18-23 Juillet 1998.
19. DELACOURTE A., DAVID J.P., BUEE L., WATTEZ A., SERGEANT N., VERMERCH P., GHOZALI F., FALLET-BIANCO C., PASQUIER F., LEBERT F., PETIT H., DIMENZA C. Criteria to establish a biochemical (postmortem) diagnosis of AlzheimerÕs disease: CEBDAD. European J of Neurology 1998;5suppl3:S2
20. DELACOURTE A., DAVID J.P., BUEE L., WATTEZ A., PASQUIER F., LEBERT F. Criteria to establish a biochemical (postmortem) diagnosis of AlzheimerÕs disease. Society for Neuroscience, Los Angeles, USA, 7-12 novembre 1998.
21. Feirrerra, S., Dupont-Wallois, L., Soulié C., Delacourte A. and Caillet-Boudin M-L. Cellular model of Alzheimer-type neuronal degeneration. Neurological Workshop. Nov. 98. Rev. Neurol, 1998, 3S15-3S16
22. MAILLIOT C., PODEVIN-DIMSTER V., FISKUM G., DELACOURTE A., BUEE L. Differential phosphorylation of the cerebral tau isoform in a canine model of cerebral ischemia/reperfusion. Sixth International Conference on Alzheimer's disease and related disorders, Amsterdam, 18-23 Juillet 1998.
23. MAILLIOT C., PODEVIN-DIMSTER V., FISKUM G., DELACOURTE A., BUEE L. Differential phosphorylation of the cerebral tau isoform in a canine model of cerebral ischemia / reperfusion. 2ème journée de LARC - Neurosciences. Univ. Caen, 2 octobre 1998.
24. MAILLIOT C., SERGEANT N., BUSSIERE T., DELACOURTE A., BUEE L. Different sets of phosphorylated tau isoforms aggregate into filaments in neurodegenerative disorders allowing a differential biochemical diagnosis. Society for Neuroscience, Los Angeles, USA, 7-12 novembre 1998.
25. Maillot C, Bussière T, David JP, Wattez A, Dupire MJ, Caillet-Boudin ML, Di Menza C, Pasquier F, Lebert F, Petit H, Delacourte A, Buée L. Molecular diagnosis of neurodegenerative disorders: focusin on tau proteins. Lille Neurological Worksop. 27-28 novembre 1998. Prix du meilleur poster. Rev. Neurol, 1998, 3S20-3S21
26. Soulié C, Valérie Mitchell, Jean-Claude Beauvillain, André Delacourte, Marie-Laure Caillet-Boudin. Human SKNSH-SY 5Y neuroblastoma cells: Apolipoprotein E and cell differentiation. Society for neuroscience, Washington, USA, Novembre 98.