Abstract
Alzheimer’s disease, the most common neurodegenerative disease, is characterized by a progressive loss of synapses and accumulation of amyloid-beta (Aβ) peptides in the brain. Previous studies demonstrated that acute increase in synaptic activity in cultured hippocampal slices and mouse brains (Cirrito et al. Neuron 48: 913–922, 2005; Kamenetz et al. Neuron 37: 925–937, 2003) enhanced secretion of Aβ. Since synaptic activity promotes Aβ secretion, it could also affect the trafficking and processing of its precursor, the amyloid precursor protein (APP). Here, we describe a method to investigate the effect of acute synaptic activation on APP trafficking within dendrites.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR, May PC, Schoepp DD, Paul SM, Mennerick S, Holtzman DM. (2005) Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron, 48(6):913–922.
Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, Sisodia S, Malinow R. (2003) APP processing and synaptic function. Neuron, 37(6):925–937.
Tampellini D, Rahman N, Gallo EF, Huang Z, Dumont M, Capetillo-Zarate E, Ma T, Zheng R, Lu B, Nanus DM et al. (2009) Synaptic activity reduces intraneuronal Abeta, promotes APP transport to synapses, and protects against Abeta-related synaptic alterations. J Neurosci, 29(31):9704–9713.
Takahashi RH, Almeida CG, Kearney PF, Yu F, Lin MT, Milner TA, Gouras GK. (2004) Oligomerization of Alzheimer’s beta-amyloid within processes and synapses of cultured neurons and brain. J Neurosci, 24(14):3592–3599.
Koo EH, Squazzo SL. (1994) Evidence that production and release of amyloid beta-protein involves the endocytic pathway. J Biol Chem, 269(26):17386–17389.
Ehlers MD. (2003) Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system. Nat Neurosci, 6(3):231–242.
Lu W, Man H, Ju W, Trimble WS, MacDonald JF, Wang YT. (2001) Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons. Neuron, 29(1):243–254.
Kaether C, Skehel P, Dotti CG. (2000) Axonal membrane proteins are transported in distinct carriers: a two-color video microscopy study in cultured hippocampal neurons. Mol Biol Cell, 11(4):1213–1224.
Tampellini D, Magrane J, Takahashi RH, Li F, Lin MT, Almeida CG, Gouras GK. (2007) Internalized antibodies to the Abeta domain of APP reduce neuronal Abeta and protect against synaptic alterations. J Biol Chem, 282(26):18895–18906.
Acknowledgments
Supported by an Alzheimer’s Association New Investigator Award (DT) and Zenith Award (GKG) and National Institute of Health grants AG027140 and AG028174 (GKG). We thank Dr. Carlos Dotti, Catholic University of Leuven, Belgium, for providing the APP–YFP construct.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Tampellini, D., Gouras, G.K. (2011). Analysis of Vesicular Trafficking in Primary Neurons by Live Imaging. In: Manfredi, G., Kawamata, H. (eds) Neurodegeneration. Methods in Molecular Biology, vol 793. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-328-8_22
Download citation
DOI: https://doi.org/10.1007/978-1-61779-328-8_22
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-327-1
Online ISBN: 978-1-61779-328-8
eBook Packages: Springer Protocols