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Can a gene linked to Alzheimer’s cause damage to the nerve cells by producing abnormal levels of fat in brain cells?
Sarah Cohen
University of North Carolina
Chapel Hill, NC - United States
Background
Brain cells (in particular, nerve cells) need lipids (fats) for energy and for maintaining their structures. As a result, the process by which fat is produced and transported to these cells is vital for the proper function of the brain. Nerve cells receive fats from “helper” cells called astrocytes, and this transportation process involves several proteins, including apolipoprotein E (ApoE).
Apolipoprotein E (APOE) is a gene that can produce several different versions of the ApoE protein. According to many studies, one version of the APOE gene called APOE-e4 is a known risk factor for Alzheimer’s. While the reasons behind this increased risk are unclear, other studies have found that astrocytes carrying APOE-e4 produce higher than normal levels of certain fats. These “high fat” astrocytes may transport too much fat — or the wrong kinds of fat — to brain cells, which in turn might lead to brain cell damage and death in Alzheimer’s.
Research Plan
Dr. Sarah Cohen and colleagues will explore the potential link between APOE-related fat abnormalities and the risk of dementia. First, they will engineer different types of astrocytes from adult human stem cells called induced pluripotent stem cell (iPSC), which can be reprogrammed to develop into any type of cell within the human body. Some of these astrocytes will be genetically engineered to carry the APOE-e4 version, while others will carry another version of APOE (APOE-e3) that does not increase Alzheimer’s risk. The researchers will then assess how astrocytes containing different APOE forms vary in how they produce lipids and in how they transport them to other cells.
Impact
The results of this study could shed new light on how APOE may affect an individual’s risk for Alzheimer’s through the fat transport in astrocytes. It could also identify novel targets for therapies that prevent or delay the onset of Alzheimer’s.
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