My research is focused on understanding how intracellular trafficking is important for neuronal function in aging and Alzheimer´s disease (AD). Early in AD neurons responsible for the formation of memories start to malfunction. The trigger for neuronal degeneration in AD is the toxic peptide beta-amyloid, a sticky peptide that accumulates with aging. However, in late-onset AD it is not clear whether beta-amyloid accumulation is due to increased production of the highly reactive 42 amino acid long beta-amyloid. Among the novel putative genetic risk factors for late-onset AD are regulators of endocytic trafficking. Endocytic trafficking of the amyloid precursor protein (APP) and of APP secretases, especially BACE1, are key for beta-amyloid production at endosomes. Recently, we discovered that two late-onset AD risk factors, Bin1 and CD2AP, loss of function deregulate the endocytic trafficking in neurons of amyloid precursor protein and its first cleavage enzyme (BACE1), leading to increased beta-amyloid production.

Now we are investigating the impact of AD variants in Bin1 and CD2AP function. We are investigating neuronal aging because old age is the most important risk factor for late-onset AD. In the lab, we discovered neuronal aging alterations in endocytosis, and are working to determine its impact into aging-synaptic decline. We use unique aging cellular systems with comprehensive advanced quantitative dynamic imaging, proteomics, and neurosciences.

Keywords: Neuroscience, Cell biology, Alzheimer's disease, Intracellular trafficking