COGNOS.AD · Memory and learning in Alzheimer's disease: involvement of amyloid precursor protein and tau in function and dysfunction of the hippocampal formation
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-02-01 → 2007-01-31
- EU contribution
- €152,752
- Participants
- 1
- Scheme
- EIF
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - COGNOS.AD (Memory and learning in Alzheimer's disease: involvement of amyloid precursor protein and tau in function and dysfunction of the hippocampal formation)
Protein tau is a major microtubule-associated protein in the vertebrate nervous system. Differential phosphorylation and isoform expression of tau are believed to regulate the assembly and stabilisation of microtubuli. Alzheimer's disease, frontotemporal dementia (FTD) and many other neurodegenerative diseases that manifest late in life are characterised by neurofibrillar inclusions of highly phosphorylated protein tau. In this project, tau and two of its most important kinases were characterised in different contexts and several new functions were determined. Expression of tau was shown to suppress proliferation, promote neuronal differentiation and restore neurite and axonal outgrowth in the hippocampus of a tau knockin-knockout mouse model. Overexpression of tau kinase cdk5 activator p25 resulted in gliosis. As astroglia and microglia fuelled inflammation, rapid neurodegeneration lead to hippocamapal sclerosis. Not only GSK3-beta, but also its isoenzyme GSK3-alpha were shown to increase tau phosphorylation. Another effect of GSK3-beta over-expression was the impeded transport of synaptically active a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors to the cell surface after glycine stimulation, indicating negative effects on long-term potentiation and cognition.
Data: CORDIS, © European Union
Project objective
Alzheimer's disease (AD) is the most common cause of dementia in the Western world, accounting for up to 50-60% of all late-onset dementia cases. Neuropathologically, AD is characterised by abnormal accumulations of intracellular neurofibrillary tangles and extra-cellular amyloid plaques in the brain; additional features are deficits in multiple neurotransmitter signalling systems and synaptic loss. The objectives of this proposal are to study transgenic mouse models to define molecular mechanisms leading to amyloid and tau pathology and examine at what level they impact the normal signalling pathways of cognition.Our basic aims are to(i) investigate proliferation, neural differentiation, cell renewal, survival and synaptic plasticity in(ii) highly relevant single or multiple transgenic AD mouse models with amyloidoses and tauopathies,(iii) assess cognition, learning, memory and behaviour in the same mouse models and (iv) devise therapies to improve any deficiencies.We expect the research outlined in this proposal to:(i) increase our understanding of amyloid and tau pathology, enabling us(ii) to explore diagnostic biomarkers and drug targets for AD and(iii) to contribute to the fundamental knowledge of neuro-degenerative disease.
Original text from CORDIS.
Participants
- KATHOLIEKE UNIVERSITEIT LEUVEN · LEUVENCoordinatorBelgium
Links
Data: CORDIS, © European Union