Contact:
ZMBH, Im Neuenheimer Feld 282
69120 Heidelberg, Germany
Tel.: + 49-6221 54 6847
Fax.: +49-6221 54 5891
s.kins@zmbh.uni-heidelberg.de

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:

1. 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.

2. We found that APP/APLPs function as cell adhesion molecules and investigate the resulting physiological and pathogenic consequences of APP/APLPs malfunction.

Thanks for funding our research to the DFG, Fritz Thyssen-Stiftung, Landesstiftung Baden-Württemberg, Hans und Ilse Breuer Stiftung, DAAD and Alzheimer Forschung Initiative (AFI).

Selected Publications

1) Back, S., Haas, P., Tschäpe, J.-A., Gruebl, T., Kirsch, J., Müller, U., Beyreuther, K., Kins, S.# In neurons APP can be transported independent of any sorting signal to the axonal and dendritic compartment. J. Neurosci. Res., in press.
2) Rusu, P., Jansen, A., Soba, P., Kirsch, J., Löwer, A., Merdes, G., Kuan, Y.-H., Jung, A., Beyreuther, K., Kjaerulff, O., Kins, S.#. Axonopathy in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity, Eur. J. Neurosci. 2007 Feb; 25 (4): 1079-86.
3) Kuan, Y.-H., Grübl, T., Soba, P., Eggert, S., Nesic, I., Kirsch, J., Beyreuther, K., Kins, S.#. The processing and anterograde transport of APP, APLP1 and APLP2 is affected by the carboxyl-terminal binding partner PAT1a J. Biol. Chem., 2006, 281(52), 40114-123.
4) Kins, S.#, Lauther, N., Szodorai, A., and Beyreuther, K. Subcellular trafficking of the APP gene family and its pathogenic role in Alzheimer’s Disease. Neurodegener Dis. 2006; 3 (4-5), 218-26.
5) Kins, S. #, Beyreuther, K. Teasing out the tangles. Nat. Med., 2006; 12(7), 764-765.
6) Soba, P., Eggert, S., Wagner, K., Zentgraf, H., Siehl, K., Kreger, S., Lower, A., Langer, A., Merdes, G., Paro, R., Masters, C.L., Muller, U., Kins, S.*, Beyreuther, K.*, Cell interactions are promoted by trans-dimerization of APP family members, arranged as homo- or hetero-complexes in synaptic membranes. EMBO J., 2005, 24, 3624-36.
7) Lazarov, O., Morfini, G.A., Szodorai, A., Kins, S., Lee, V., Trojanowski, J., Price, D., Brady, S.T., Sisodia, S.S.  Axonal Transport, APP, Kinesin and the Processing Apparatus: Revisited. J. Neurosci. 2005, 25, 2386-95.
8) Kins, S., Kurosinski, P., Nitsch, R.M. and Götz, J. Hyperphosphorylation and somatodendritic localization of tau in PP2A dominant negative mutant mice is associated with activation of ERK and JNK signaling. J. Am. Path., 2003, 163 (3), 833-843.
9) Kins, S., Betz, H., and Kirsch, J. Collybistin, a newly identified brain-specific GEF, induces submembrane clustering of gephyrin. Nat Neurosci 2000, 3, 22-29.

*equal contribution
#corresponding author