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Alzheimer's-linked apolipoprotein E produced by neurons, Gladstone study

Scientists at the Gladstone Institute of Neurological Disease have now proved using a specialized mouse model that the controversial protein, apolipoprotein E, is indeed produced by neurons.// The results of this study have for the first time established a definitive association between the two.

Also known as apoE, this cholesterol-carrying protein has three common forms, one of which, apoE4, is the major known genetic risk factor for Alzheimer's disease, according to studies published around the world in recent years. Until now, most researchers have believed that apoE is synthesized in the brain solely in such cells as astrocytes, microglia, and ependymal layer cells. Controversial for the last decade has been the question of whether or not neurons, which make thought and memory possible by transmitting electrical signals, can produce apoE.

The Gladstone study, published in the May 10 issue of the Journal of Neuroscience and highlighted in its ‘This Week in the Journal’ section, proves that neurons, too, produce apoE, but only in response to injury to the brain.

Key to the finding has been the development of a mouse model that is uniquely capable of alerting researchers whenever and wherever the apoE gene is expressed. Huang and his team have succeeded in making one of the two alleles of the apoE gene produce a green fluorescent protein that represents apoE, while the remaining allele functions normally. Thus, under a microscope, the bright green fluorescence, dubbed EGFPapoE, shows researchers wherever the apoE gene is expressed.

‘This study lays to rest a long-standing controversy concerning the neuronal expression of apoE,’ says senior author Huang, an assistant professor of pathology and neurology at UCSF. ‘Our study proves clearly that neurons produce apoE in response to injury. They support the notion that an understanding of how apoE expression is regulated in neurons is important for unraveling the mechanisms
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