Neuroscience 2003 Abstract
| Presentation Number: | 809.15 |
|---|---|
| Abstract Title: | An investigation into apoE4 related synaptic deficits in human apoE targeted replacement mice. |
| Authors: |
Mace, B.*1,2
; Moss, J.1,2
; Farrell, J.1,2
; Schmechel, D.1,2
; Sullivan, P.1,2
1Med., Duke Univ., Durham, NC 2Bryan Alzheimer's Dis. Res. Ctr., Duke Univ., Durham, NC |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Synaptic Plasticity -- Other |
| Secondary Theme and Topics | Cognition and Behavior<br />- Animal Cognition and Behavior<br />-- Cognitive learning and memory systems |
| Session: |
809. Spines & Synaptogenesis II Poster |
| Presentation Time: | Wednesday, November 12, 2003 10:00 AM-11:00 AM |
| Location: | Morial Convention Center - Hall F-I, Board # F42 |
| Keywords: | Alzheimer's disease, LTP, transgenic, acetylcholine esterase |
The human apolipoprotein (apo) E4 allele is associated with an early age of onset and increased risk of Alzheimer’s disease (AD). It has been proposed that apoE functions to maintain synaptic integrity in the central nervous system which is supported by studies revealing apoE isoform specific effects in calcium homeostasis, synaptic transmission, and behavior in various animal models. Studies from our lab and two of our collaborators, using a human apoE targeted replacement (TR) mouse model system, provide additional evidence for apoE’s role in synaptic integrity. We previously presented work (SFN 2002 meeting) showing significantly reduced synaptic activity and stunted neuronal morphology in apoE4 compared to apoE3 mice. Our collaboration with Grootendorst et al. shows apoE4 deficits in behavior for spatial and working memory, compared to apoE3. Our collaboration with Trommer et al. demonstrates there is significantly less LTP in apoE4 compared to apoE3 mice. All groups used male human apoE3 and E4 TR mice backcrossed 8 generations for strain purity. Together these data suggest there are inherent deficits in synaptic integrity in the apoE4 mice. We have observed an age dependent decline in cholinergic transmission in the apoE4 mice (compared to apoE3 mice) using histological techniques for measuring acetylcholine esterase activity, and immunocytochemical techniques for analyzing vesicular choline acetytransferase expression. We are examining these same animals with silver staining methods as well as quantitative measures of specific brain lipids associated with modulating synapse function. We propose that some of the observed apoE4 synaptic deficits can be explained by alterations in cholesterol and fatty acid metabolism at the synaptic cleft.
Supported by Bryan Alzheimer's Disease Research Center Project Grant
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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