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Nat Rev Neurosci. 2017 May;18(5):281-298. doi: 10.1038/nrn.2017.29. Epub 2017 Mar 31.

Not just amyloid: physiological functions of the amyloid precursor protein family.

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Ruprecht-Karls University Heidelberg, Institute of Pharmacy and Molecular Biotechnology, Bioinformatics and Functional Genomics, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
Goethe University Frankfurt, Institute of Clinical Neuroanatomy, Neuroscience Center, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
TU Braunschweig, Zoological Institute, Cellular Neurobiology, Spielmannstrasse 7, D-38106 Raunschweig, Germany.
Helmholtz Centre for Infection Research, Neuroinflammation and Neurodegeneration Group, Inhoffenstrasse 7, 38124 Braunschweig, Germany.


Amyloid precursor protein (APP) gives rise to the amyloid-β peptide and thus has a key role in the pathogenesis of Alzheimer disease. By contrast, the physiological functions of APP and the closely related APP-like proteins (APLPs) remain less well understood. Studying these physiological functions has been challenging and has required a careful long-term strategy, including the analysis of different App-knockout and Aplp-knockout mice. In this Review, we summarize these findings, focusing on the in vivo roles of APP family members and their processing products for CNS development, synapse formation and function, brain injury and neuroprotection, as well as ageing. In addition, we discuss the implications of APP physiology for therapeutic approaches.

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