Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with synaptic dysfunction, pathological accumulation of beta-amyloid (Abeta), and neuronal loss. The self-association of Abeta monomers into soluble oligomers seems to be crucial for the development of neurotoxicity (J. Neurochem., 00, 2007 and 1172). Abeta oligomers have been suggested to compromise neuronal functions in AD by reducing the expression levels of the CREB target gene and brain-derived neurotrophic factor (BDNF) (J. Neurosci., 27, 2007 and 2628; Neurobiol. Aging, 36, 2015 and 20406 Mol. Neurodegener., 6, 2011 and 60). We previously reported a broad neuroprotective activity of physiological Abeta monomers, involving the activation of type-1 insulin-like growth factor receptors (IGF-IRs) (J. Neurosci., 29, 2009 and 10582, Front Cell Neurosci., 9, 2015 and 297). We now provide evidence that Abeta monomers, by activating the IGF-IR-stimulated PI3-K/AKT pathway, induce the activation of CREB in neurons and sustain BDNF transcription and release.

*** IBB - CNR ***

Institute of Biostructures and Bioimaging, National Council of Research (IBB-CNR), Via Paolo Gaifami 18, 95126, Catania, Italy., Endocrinology, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Medical Center, University of Catania, via Palermo 636, 95122, Catania, Italy., Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125, Catania, Italy., Department of Chemical Sciences, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.,

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