1. Control/Tracking Number: 2015-S-3595-SfN
Activity: Scientific Abstract
Current Date/Time: 5/11/2015 3:23:41 PM
Memory dysfunction in a rat model of Alzheimer’s disease.
AUTHOR BLOCK: *C. R. GALLOWAY1, M. L. AIREY2, K. RAVIPATI2, R. M. COHEN3,
A. I. LEVEY4, J. R. MANNS1;
1Psychology, 2Neurosci. and Behavioral Biol. Program, 3Psychiatry, 4Neurol., Emory Univ.,
Atlanta, GA
Abstract:
Alzheimer’s disease (AD) is a growing health problem that affects millions of people, but current
treatment options are limited. Many new candidate drug treatments have demonstrated efficacy
in transgenic mouse models of AD, but ultimately fail in the clinic. One potential reason for the
difficulty in translating preclinical findings into viable drug treatments for AD may be due to the
differences between pathological features of human AD, such as tau pathology and cell death,
and the pathology of transgenic AD mouse models that do not show these features. Recently, a
transgenic rat model of Alzheimer’s disease (TgF344 rats) with human APPSwe and PS1ΔE9
mutations was developed (Cohen et al., 2013, J. Neurosci., 33: 6245-6256). Like mouse models
of AD, TgF344 rats develop age-dependent build-up of amyloid pathology, such as soluble Aβ42
and plaques. Unlike mouse models of AD, TgF344 rats also develop tau pathology and profound
cell death, making them a good model to probe questions about AD that may be more readily
translatable to human AD. Moreover, using a rat model of AD will increase the feasibility of
using high-density in vivo electrophysiology to answer questions about how hippocampal
dysfunction contributes to memory loss symptoms in AD. It was previously shown that TgF344
rats had intact spatial memory performance at 6 months of age but performed poorly on a spatial
memory task at 16 months. In order to further understand this rat model of AD, in the current
study we asked at what age between 6 and 16 months the TgF344 rats would show memory
impairments, and whether spatial memory and non-spatial memory would be differentially
impaired. 16 female Tg344 rats were tested monthly, beginning at 5 months of age, on a non-
spatial and a spatial recognition memory task. We found that TgF344 AD rats (n=8) had
impaired spatial recognition memory performance by 9-12 months of age relative to wild-type
(WT; n=8) littermate controls. In contrast, TgF344 AD rats performed similarly to WT controls
on the spatial memory task from 5-8 months of age and on the non-spatial recognition memory
task from 5-12 months. The selective memory impairment of TgF344 AD rats from 9-12 months
supports an important role of spatial memory dysfunction relatively early in the disease process.
Subsequent studies will use in vivo electrophysiological recordings in the hippocampus to ask if
TgF344 AD rats have dysfunctional neural representations of space (e.g. “place fields”), and, if
so, whether systemic administration of a muscarinic acetylcholine receptor agonist might
attenuate the dysfunction.
:
Presentation Preference (Complete): Poster Only
Linking Group (Complete): None selected

2. Nanosymposium Information (Complete):
Theme and Topic (Complete): C.02.v. Cognitive function ; C.02.b. APP/Abeta: Animal
models
Keyword (Complete): ALZHEIMER'S DISEASE ; HIPPOCAMPUS ; MEMORY
Support (Complete):
Support: Yes
Grant/Other Support: : NIH Grant 1R21AG042730-01A1
Finalized Abstracts : Finalized
Special Requests (Complete):
Would you be interested in being considered for a dynamic poster?: No, I am not
interested in presenting a Dynamic Poster
Is the submitting author of this abstract also a senior author?: No
Is the first (presenting) author of this abstract a high school or undergraduate student?:
None
Religious Conflict?: No Religious Conflict
Additional Conflict?: No
Status: Finalized