Journal
JOURNAL OF NEUROSCIENCE
Volume 34, Issue 37, Pages 12313-12327Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2255-14.2014
Keywords
beta-amyloid; A beta; amyloid precursor protein; APP; axonal targeting; dendritic targeting
Categories
Funding
- Adler Foundation
- Edward H. Levy Fund Cure Alzheimer's Fund
- NIH/NINDS [P30 NS061777]
- NIA [F30AG034001]
Ask authors/readers for more resources
The beta-amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimer's disease. APP is processed in neurons, but little is known about the relative contributions of presynaptic or postsynaptic compartments to the release of A beta peptides. To address this issue, we transduced primary neurons from Sprague-Dawley rats or APP(-/-) mice (B6.129S7-App(tm1Dbo)/J) with lentiviral constructs expressing APP chimeras harboring targeting motifs from low-density lipoprotein receptor or neuron-glia cell-adhesion molecule to polarize expression to either dendritic or axonal membranes, respectively. Using imaging and quantitative biochemical approaches, we now report that APP selectively targeted to either axons or dendrites leads to the secretion of full-length A beta peptides with significantly elevated release from dendritic compartments. These findings reveal that the enzymatic machinery required for production of A beta peptides are operative both in presynaptic and postsynaptic compartments of primary neurons, leading to the suggestion that A beta-mediated impairments in glutamatergic neurotransmission is the result of A beta release from both local and distal neuronal compartments.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available