CV of Delacourte Andre

1985-2005: Head of the research group "Aging and neuronal degeneration " constituted by 30 members, including staff members from INSERM and CNRS, staff members from Lille University of Medicine (neurologists, biochemists, geriatrists) and students (scientific and medical fields).

Dr André Delacourte is a staff scientist (Director of Research INSERM) in the INSERM Research Center 815 of Lille, France. Dr Delacourte received his higher education and Ph.D from the University of Sciences in Lille, France. He leads a team working on the different biochemical aspects of neurodegenerative disorders.

Dr Delacourte was a pionner in the biochemical characterization of PHF, a hallmark of Alzheimer's disease. He was the first to describe the concept of pathological tau proteins (1989), to describe the different biochemical signatures of tau proteins in Alzheimer's disease (1989: Tau 64 and 69, 1990: tau 60; 1997: tau 74); progressive supranuclear palsy and corticobasal degeneration (1991); Pick's disease (1996), myotonic dystrophy (1996) (references in Medline). Recently, Dr Delacourte' team discovered the genetic mechanisms involving the abnormal tau splicing in myotonic dystrophy (DM1) (see Sergeant et al, 2001).

Dr Delacourte gave the explanation for these different biochemical tau phenotypes: tau lesions are made of aggregates of different sets of tau isoforms. He classified these different tau pathologies in classes (class I for Alzheimer and related diseases; class II for progressive supranuclear palsy, with aggregation of exon 10 plus- tau isoforms; class III for Pick's disease with aggregation of exon 10 minus-tau isoforms; class IV for myotonic dystrophy (as described in Delacourte A, Buée L. Tau pathology: a marker of neurodegenerative disorders. Current Opinion in Neurology 2000;13:371-376). These different tau pathologies have been modelled in cell cultures (Mailliot et al, FEBS Lett 1998;433:201-4).

Dr Delacourte also described for the first time the biochemical pathway of tau pathology in aging and Alzheimer's disease (Delacourte A et al, The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease. Neurology 1999;52:1158-1165. For that purpose, he used a prospective and multidisciplinary approach, and worked on 130 non-demented and demented cases. These results allow to propose, for the first time, biochemical criteria for the diagnosis of Alzheimer's disease (CEBDAD), that will help to find new markers and to develop a biological test for the ante mortem and early diagnosis of Alzheimer's disease (Delacourte A et al Neurology 1999;52:1158-1165). These results will also open a possibility to understand the relationship between amyloid and tau pathologies, the key to understand and cure Alzheimer's disease.

A. Delacourte described the natural and molecular history of many neurodegenerative disorders, and especially non-FAD (familial autosomic dominant) Alzheimer's disease, that represents more than 99% of all Alzheimer cases (Delacourte, Neurology, 2002). The data published by Dr Delacourte should be helpful for therapeutical and diagnostic perspectives, as well as for the development of relevant animal models, bearing in mind that models are useful when they really mimic the molecular dysfunctions found in the affected human brain. All these results open new therapeutic avenues, that are currently set up.

Indeed, the knowledge of the human biochemistry of amyloidosis is opening a new approach of vaccination, more straigthforward, and with less possible side effects: vaccination against the pathological N-truncation of Ab peptide.

Andre Delacourte, Lille, France

Inserm Unit 815, Lille France.

The global strategy of the team is to understand the natural and molecular history of sporadic Alzheimer’s disease in order to improve cellular and animal models for drug discovery.

Among the discoveries of his team,

the description of the bar-code of sporadic tauopathies that distinguishes different types of degenerating processes leading to cognitive impairment: Alzheimer’s disease (AD) dementia with parkinsonism (PSP, CBD), Pick’s disease, myotonic dystrophy.
The staging of tau and amyloid pathologies in sporadic Alzheimer’s disease, showing that both processes are in synergy to provoke neurodegeneration
The discovery that the seeds of amyloid plaques are pathological N-truncated Abeta peptides that are therapeutic targets for a vaccination approach.
The demonstration that APP intra cellular products, potential neurotrophic factors, are early decreased in AD
The finding of a new family of APP-modulating drugs that have huge anti-Alzheimer potential.
The demonstration that APP is also a therapeutic target for Lewy body dementia