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Unraveling genetic risk factors for Alzheimer's disease

Study suggests promoting conversion of glucose into brain energy could reduce risk or delay disease onset in risk gene carriers

Society for Neuroscience

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IMAGE: Pictured from right to left are first and second authors Long Wu and Xin Zhang. view more 

Credit: Liqin Zhao

The strongest genetic risk factor for Alzheimer's disease may impair the brain's ability to convert its primary fuel source into usable energy, finds a study of female mice published in JNeurosci. The research suggests therapeutic strategies that promote brain energy conversion in risk gene carriers could help to reduce risk or delay onset of the disease.

Approximately 20 percent of people produce a version of human apolipoprotein E called ApoE4, which increases their risk of developing Alzheimer's disease, while the five percent of people who produce the rare ApoE2 appear to show some protection against Alzheimer's.

Liqin Zhao and colleagues explored the influence of these ApoE variations -- in addition to the most common ApoE3 that does not confer risk for or protection against Alzheimer's disease -- on the chemical reactions that transform glucose and ketone bodies into the form of energy used by cells. The brains expressing the three types of proteins handled the process differently, which may underlie their distinct effects on Alzheimer's risk and protection. While the ApoE4 brains struggled to use glucose, they appeared to utilize ketone bodies -- the brain's secondary fuel source -- to compensate for the energy deficiency.

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Article: Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention
DOI: https://doi.org/10.1523/JNEUROSCI.2262-17.2018
Corresponding author: Liqin Zhao (University of Kansas, Lawrence, USA), lzhao@ku.edu

About JNeurosci

JNeurosci, the Society for Neuroscience's first journal, was launched in 1981 as a means to communicate the findings of the highest quality neuroscience research to the growing field. Today, the journal remains committed to publishing cutting-edge neuroscience that will have an immediate and lasting scientific impact, while responding to authors' changing publishing needs, representing breadth of the field and diversity in authorship.

About The Society for Neuroscience

The Society for Neuroscience is the world's largest organization of scientists and physicians devoted to understanding the brain and nervous system. The nonprofit organization, founded in 1969, now has nearly 37,000 members in more than 90 countries and over 130 chapters worldwide.

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