LECTURE PRESENTATION Open Access

Deciphering the role of APP in synaptic functionHui Zheng

From 2011 International Conference on Molecular NeurodegenerationShanghai, China. 22-24 September 2011

BackgroundGenetic and biochemical studies establish a central role ofthe amyloid precursor protein (APP) in Alzheimer’s disease(AD): genetic mutations and gene amplification of APP arelinked to a subset of early onset familial Alzheimer’s dis-ease (FAD), and APP processing generates b-amyloid (Ab)peptides, which are the principal components of the amy-loid plaque pathology. Although b-amyloid plaques are thehallmark of AD, synaptic dysfunction closely correlateswith cognitive impairment and is recognized as a causalevent leading to AD pathogenesis. Since Ab is naturallygenerated along with other products through APP proces-sing, investigating the role of APP and its cleavage productsin synaptic function and dysfunction is critically importantin understanding AD pathogenesis.

ResultsWe seek to understand the physiological functions of APPin neurons and synapses using in vivo mouse models andin vitro culture systems. Analysis of the APP knockoutmice allows us to identify a functional role of APP insynaptic plasticity and learning and memory. Our investi-gation of mice deficient in APP and its homolog APLP2establishes an essential role of APP family protein in med-iating cholinergic synaptic structure and neurotransmis-sion in both peripheral neuromuscular synapse andcentral cholinergic neurons. By creating an APP condi-tional allele, we demonstrate that APP is required in bothpre- and postsynaptic terminals; and that pre- and postsy-naptic APP interact to mediate synaptic structure andfunction. These in vivo findings are supported by in vitromixed-culture studies, which reveal that APP potentlyinduces synaptogenesis. Independent of the synaptic adhe-sion property that requires the full-length protein, wefound that the soluble secreted APP ectodomain mediatestranscription of genes related to aging and amyloidsequestration.

ConclusionOur studies identify APP as synaptic adhesion and signal-ing molecules, which are mediated by distinct functionaldomains. Perturbation of these activities may contribute tosynaptic dysfunction and AD pathogenesis.

Published: 7 February 2012

doi:10.1186/1750-1326-7-S1-L7Cite this article as: Zheng: Deciphering the role of APP in synapticfunction. Molecular Neurodegeneration 2012 7(Suppl 1):L7.

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Submit your manuscript at www.biomedcentral.com/submitHuffington Center on Aging, Department of Molecular and Human Genetics,

Baylor College of Medicine, Houston, Texas, USA

Zheng Molecular Neurodegeneration 2012, 7(Suppl 1):L7http://www.molecularneurodegeneration.com/content/7/S1/L7

© 2012 Zheng; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.