No hippocampal neuron or synaptic bouton loss in learning-impaired aged β-Amyloid precursor protein-null mice
Section snippets
Animals
APP-null mice (B6129-App) (n=12) and control B6129 mice (n=11) were produced from interbreeding of hemizygous (APP+/−mice) [50% B6 and 50% 129/Sv(ev)] and were aged at the Merck Research Laboratories, Rahway, NJ, U.S.A.65 A subpopulation (approximately 15%) of APP-null mice suffer from seizures (primarily caused by disturbance) and/or lethargy (inactivity and non-responsiveness), and were not included in this study since they die within the first 12 months of age. Seizure activity and lethargy
Results
Aged (18–28-months-old) APP-null mice had a 14.7% lower mean body weight than age-matched control mice (controls: 38.7±1.8 g; APP-null: 33.0±2.2 g). This difference however did not reach statistical significance (P=0.06). A similar body weight difference has also been reported between three-month-old APP-null mice and controls.65 Based upon the limited data available there was no indication for a difference in the mean lifespan of APP-null mice when the subgroup which is epileptic and lethargic
Discussion
In the present study we provide further evidence for a role of APP in learning and memory. Aged APP-null mice revealed a learning impairment in the Morris water maze most evident on the first and last day of acquisition. On the second day of acquisition, APP-null mice showed some learning but their performance never reached that of age-matched controls. In the probe trial, APP-null mice did not show a spatial preference for the old goal platform location. This lack of spatial strategy is also
Conclusion
The cognitive deficits observed in Alzheimer's disease (AD) have been linked to several types of neurodegeneration including neuron and synapse loss. Mutations in the APP gene have been identified which alter processing of APP and cause familial AD.17., 49. A loss of the normal function of APP in AD brain cannot be excluded and may contribute to the AD dementia. However, our results suggest that the lack of APP does not lead to significant synaptic bouton and neuron loss, implying that the
Acknowledgements
The authors would like to thank Dr J. Long (GRC, NIA, Baltimore, U.S.A.) for comments on this manuscript, and D. Kurth, R. Lang, C. Bauer, and H. Zysset for technical assistance. We would also like to thank Drs L. Binder (Northwestern University Medical School, Chicago, U.S.A.) and M. Staufenbiel (Novartis Pharma, Basel, Switzerland) for the gift of antibodies. This work was supported by grants from the Swiss National Science Foundation (31-44526.95 and 31-46612.96) and the Swiss Life
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