AI Article Synopsis
- ApoE4 is linked to cognitive decline and is a significant genetic risk factor for Alzheimer's disease (AD).
- Research using mouse models showed that removing apoE4 from astrocytes didn’t prevent learning and memory issues, but removing it from neurons did offer protection.
- The study identifies GABAergic interneurons as critical in the negative effects of apoE4, suggesting they could be a new target for AD treatments.
Article Abstract
Apolipoprotein (apo) E4 is expressed in many types of brain cells, is associated with age-dependent decline of learning and memory in humans, and is the major genetic risk factor for AD. To determine whether the detrimental effects of apoE4 depend on its cellular sources, we generated human apoE knock-in mouse models in which the human APOE gene is conditionally deleted in astrocytes, neurons, or GABAergic interneurons. Here we report that deletion of apoE4 in astrocytes does not protect aged mice from apoE4-induced GABAergic interneuron loss and learning and memory deficits. In contrast, deletion of apoE4 in neurons does protect aged mice from both deficits. Furthermore, deletion of apoE4 in GABAergic interneurons is sufficient to gain similar protection. This study demonstrates a detrimental effect of endogenously produced apoE4 on GABAergic interneurons that leads to learning and memory deficits in mice and provides a novel target for drug development for AD related to apoE4.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198545 | PMC |
| http://dx.doi.org/10.1523/JNEUROSCI.2281-14.2014 | DOI Listing |
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