Untangling Alzheimer's disease: the relationship between neuropathology and neurocognitive-behavioral deficits, and its therapeutic significance.
Alzheimer’s disease (AD) is a progressive brain disease that causes cognitive alterations, memory loss and behavioral changes. Neuropathological hallmarks of AD include brain atrophy, and the presence of two different types of protein aggregations: tangles composed of hyperphosphorylated Tau and plaques consisting of amyloid. The neurodegenerative process in AD is initially characterized by synaptic damage accompanied by neuronal loss. Moreover, synaptic loss is one of the strongest correlates to the cognitive impairment in patients with AD. The mechanisms underlying synaptic and cognitive deficits in AD remain poorly understood. To gain further insights into these mechanisms, we will examine how the brain changes in mutant Tau mice and how Tau is involved in cognitive and behavioral processes and related brain areas. Recent studies have suggested that targeting Tau is therapeutically promising. This will be done by compounds that dephosphorylate Tau. The different compounds will be evaluated by correlating behavioral with electrophysiological outputs, and state of the art in situ visualization techniques.