Alzheimer Disease, APP function and transport
Molecular basis of Alzheimer’s Disease: The pathological and physiological function of the APP gene family. Alzheimer disease (AD) is the most common disease in elderly people. It is characterized by a progressive loss of cognitive functions, resulting in dementia. The cognitive decline is associated with the loss of neurons, reduced synaptic density, and two characteristic pathological hallmarks: neurofibrillary tangles containing the microtubule associated protein tau and extracellular plaques mainly composed of the ß-amyloid peptide (Aß) derived from the amyloid precursor protein (APP). APP is essential for normal synaptic function and its processing, which strongly depends on the intraneuronal localization, plays a major role in the etiopathology of AD.
Our research focuses on the neuronal function of the APP gene family and the molecular motor composition underlying its intracellular transport in neurons. Thereby we are mainly interested in changes of APP transport and function while aging and its consequences for AD.
Specifically our research is currently addressing the following aims, using proteomic, biochemical, immunocytochemical and video microscopic methods in different neuronal model systems:
- We determine the molecular basis of anterograde and retrograde transport of APP, whereby we investigate specifically the underlying motor composition and the influence of intracellular ligands as well as the influence of neuronal aging.
- We found that APP/APLPs function as cell adhesion molecules and investigate the resulting physiological and pathogenic consequences of APP/APLPs malfunction.
Thanks to the DFG, BioComp 3.0, DAAD, Klaus-Tschira Stiftung, and Alzheimer Forschung Initiative (AFI) for funding our research.