Intraneuronal Aβ Causes the Onset of Early Alzheimer’s Disease-Related Cognitive Deficits in Transgenic Mice
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- 1 March 2005
- journal article
- research article
- Published by Elsevier BV in Neuron
- Vol. 45 (5), 675-688
- https://doi.org/10.1016/j.neuron.2005.01.040
Abstract
Progressive memory loss and cognitive dysfunction are the hallmark clinical features of Alzheimer’s disease (AD). Identifying the molecular triggers for the onset of AD-related cognitive decline presently requires the use of suitable animal models, such as the 3xTg-AD mice, which develop both amyloid and tangle pathology. Here, we characterize the onset of learning and memory deficits in this model. We report that 2-month-old, prepathologic mice are cognitively unimpaired. The earliest cognitive impairment manifests at 4 months as a deficit in long-term retention and correlates with the accumulation of intraneuronal Aβ in the hippocampus and amygdala. Plaque or tangle pathology is not apparent at this age, suggesting that they contribute to cognitive dysfunction at later time points. Clearance of the intraneuronal Aβ pathology by immunotherapy rescues the early cognitive deficits on a hippocampal-dependent task. Reemergence of the Aβ pathology again leads to cognitive deficits. This study strongly implicates intraneuronal Aβ in the onset of cognitive dysfunction.Keywords
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