BESAD-P: Biomarkers of Early Stages of Alzheimer Disease-Prevention

 

Investigador Principal Institución

Isidro Ferrer Abizanda

Instituto Neuropatologia, Hospital Universitario de Bellvitge

Antonio Camins Espuny

Unidad de Farmacologia y Farmacognosia. Facutad de Farmacia, Universidad de Barcelona

José Antonio del Río Fernández

Instituto de Bioingeniería de Cataluña, Parque Científico Barcelona, Universidad de Barcelona

Francisco Wandosell Jurado

Centro de Biología Molecular "Severo Ochoa", UAM-CSIC

Eva Carro Díaz

Centro de Investigación, Hospital 12 de Octubre, Madrid

Manuel Portero Otin

Grupo asociado, Facultad de Medicina, IRBLLEIDA-UdL

María Jesús Bullido

Centro de Biología Molecular "Severo Ochoa", UAM-CSIC

María López de Ceballos

Instituto Cajal-CSIC

Mª Guadalupe Mengod Los Arcos

Instituto de Investigación Biomédicas de Barcelona, CSIC

Eulália Martí Puig

Genes and Disease Program, Center for Genomic Regulation (CRG) Biomedical Science Park

 

Resumen

Rather than being a specific one-off project, this work corresponds to a programme of research. It is constructed on the basis of the groups of Ciberned areas focused on Alzheimer’s disease and neurodegeneration, and a few external members, who are interested in molecular damage at very early stages (pre-clinical sages) of AD-related pathology, using optimally preserved material from human brain banks, and focusing on the detection of early biomarkers and putative targets for therapeutic intervention, with the aim of delaying or curbing disease progression.

This program may, therefore, be considered as a platform producing new practical knowledge potentially transferable to clinical groups for testing in human beings. A history of collaboration among the participants may be found in a number of common publications. The present program and sustaining network are the fruit of previous shared interests and collaborative work. It must be stressed that this is a dynamic program in which different partners can be incorporated or excluded depending on the results of follow-up auto-validation reports that will be carried out one year after starting of work. Therefore, although the plan covers three years, a rigorous evaluation will be conducted in order to optimize research in the next period.

The program is focused on the identification of transcriptome abnormalities at very early stages of AD-related pathology (Braak stage I-II) that may be serve to: 1. increase understanding of early molecular damage in key pathways; 2. identification of putative early biomarkers; and 3. identification of putative targets of therapeutic intervention geared to delay or curb disease progression. For these purposes human post-mortem brains obtained and stored under optimal conditions will be used for epigenetics, genomics, transcriptomics, lipidomics and metabolomics followed by bioinformatics processing will be used to analyze modifications at early stages of AD-related pathology. This will be followed by validation of particular altered pathways in mice models and cell lines. Already identified putative targets will be analyzed in experimental models of AD, mainly APP/PS1 mice, by using varied therapeutic approaches under randomized conditions.

The following treatment procedures will be analyzed in the present year: 1. Hormonal treatment assay: effects of estradiol; 2. β-amyloid clearance and trophic factors from choroid plexus; 3. Treatment with CB1 and CB2 cannabinoid receptor agonists; 4. Treatment with erythropoietin (Epo); 5. Treatment with JNK inhibitors; 6. Treatment with TAT-like singular -peptide libraries to modify β-amyloid production and tau hyperphosphorylation; and 7. Anti-inflammatory therapies: PK11195, ligand of the translocator protein 18kDa.

All these aspects will be conducted in collaboration with the different partners. Observations and results will be followed along the year by in-person meetings and email correspondence. Results and observations at the end of the first year will be auto-evaluated in order to actualize group composition of the program and to optimize future research.

 

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