期刊
NEURON
卷 45, 期 5, 页码 675-688出版社
CELL PRESS
DOI: 10.1016/j.neuron.2005.01.040
关键词
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资金
- NIA NIH HHS [F32 AG24035-01, AG0212982] Funding Source: Medline
- NIMH NIH HHS [MH-12526] Funding Source: Medline
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 AD 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 AD pathology by immunotherapy rescues the early cognitive deficits on a hippocampal-dependent task. Reemergence of the AD pathology again leads to cognitive deficits. This study strongly implicates intraneuronal AD in the onset of cognitive dysfunction.
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