Alzheimer’s disease (AD) is a devastating neurodegenerative disease that accounts for two thirds of all dementia cases. AD is characterized by progressive cognitive impairment, memory loss and difficulties in daily tasks. At the microscopic level the AD brain is characterized by the accumulation of two proteins in particular: Amyloid-β (Aβ), which forms plaques outside the cells, and Tau protein, which forms fibrillary tangles inside the cells. The accumulation of these two molecules leads to neuronal loss at late stages of the disease. During early stages of AD, the brain suffers a decrease in the number of synapses – connections between neurons that transmit information, which correlates better with the cognitive impairment presented by the patients. Also implicated in the progression of AD is the Wnt signalling cascade, which normally contributes to the maintenance of synapses and function of neurons, but exactly how this pathway is affected in AD has been only partially described (Figure1).
Better understanding of how AD progresses at the molecular and cellular level, especially with regard to synapse degeneration, is extremely important for finding new therapeutic targets. Thus, projects like ours are important for society as they describe fine mechanisms affected by disease, which in the future could lead to more applied or translational research. To this end, our main objective is to identify the mechanisms that regulate the activity of the Wnt signalling cascade and its effect on synapse maintenance (Figure 1).
