FOR 1332:  Physiological Functions of the APP Gene Family in the Central Nervous System

• Subject Area: Medicine
• Term: from 2010 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 138733498

The APP protein plays a key role in the pathogenesis of Alzheimer’s disease. Little is known, however, about its role for nerve cell communication in the healthy human brain. The purpose of the Research Unit is two-fold: to find out more about the protein’s physiological role for learning and memory, and to enhance the understanding of APP functions with a view to developing new therapeutic approaches to treat Alzheimer’s disease.
Alzheimer’s disease is triggered by deposits of insoluble protein aggregates that form “plaques” in the vicinity of nerve cells within the brains of Alzheimer patients. These plaques are mainly composed of the ß-amyloid peptide. The damage it inflicts on the nerve cells finally kills them. This small protein is derived via proteolysis from a much larger precursor, the amyloid precursor protein APP.
So far, the normal cell biological and physiological functions of APP and its proteolytic products are largely unknown, although APP is produced in almost all brain cells, notably in regions important for memory formation. Recently, the enzymes involved in APP processing (termed secretases) have become major therapeutic AD targets and therapeutic interference with APP processing is likely to alter physiological APP functions. Thus, there is an urgent need for a dedicated research effort aimed at understanding the functional consequences of altered levels and activity of full length APP and its various proteolytic fragments in CNS physiology.
Seven teams of scientists cooperate within the transregional Research Unit. They come from the universities of Heidelberg, Frankfurt/Main, Mainz and the technical universities of Kaiserslautern and Braunschweig. Using interdisciplinary methodological approaches the physiological functions of APP family proteins will be studied within the central nervous system from the molecular level to the intact organism. Within our highly interactive research projects we will study the role of APP family proteins in synapse formation and function, plasticity, learning and memory, neuroprotection and regeneration.

• DFG Programme: Research Units

Projects

• Alterations of synaptic and network functions in APP and APLP-deficient mice (Applicants Draguhn, Andreas ;  Korte, Martin )
• Central Project (Applicant Müller, Ulrike )
• Central Project (Applicant Müller, Ulrike )
• Investigating the roles of endogenous APP family members in stress signaling and aging (Applicants Behl, Christian ;  Kögel, Donat )
• Physiological function of APP dimers: neuronal transport, release and receptor interaction (Applicants Kins, Stefan ;  Pietrzik, Claus Ulrich )
• Proteomic analysis of the presynaptic active zone from APP/APLP mutant mice (Applicants Karas, Michael ;  Volknandt, Walter )
• Role of APP in homeostatic synaptic plasticity in the hippocampus (Applicants Deller, Thomas ;  Müller, Ulrike ;  Vlachos, Andreas )
• Structural, physiological and pathogenic features of APP/APLPs E1 domain (Applicants Kins, Stefan ;  Wild, Klemens )
• The role of the amyloid precursor protein gene family in the adult mouse CNS (Applicant Müller, Ulrike )

• Spokesperson: Professorin Dr. Ulrike Müller
• Deputy: Professor Dr. Thomas Deller