Major Discovery May Alter Thinking on Alzheimer’s Disease

Major Discovery May Alter Thinking on Alzheimer’s Disease
Investigators at the Blancette Rockefeller Neurosciences Institute (BRNI) recently discovered that the most significant genetic risk factor associated with Alzheimer's disease, the Apolipoprotein E4 (ApoE4) gene, leads to a decrease in brain synapses, which occurs frequently prior to the onset of amyloid plaques or tangles developing in Alzheimer’s patients. This discovery may alter the paradigm, treatment and prevention of the disease. In the study entitled "ApoE4 and Aβ Oligomers Reduce BDNF Expression via HDAC Nuclear Translocation," which was recently published at the Journal of Neuroscience, the investigators revealed that ApoE4 is able to reduce synapses through its interaction with the DNA that is responsible for synapse formation and maintenance. The gene raises the nuclear translocation and activity of histone deacetylases (HDACs) in human neurons. This means that by interfering with the HDACs enzymes, which work as an on/off switch for genes, the levels of DNA-programmed brain-derived neurotrophic factor (BDNF) are reduced. Consequently, it influences the formation, repairing and plasticity capacities of brain cell synapses. The loss of mature, functional synapses is a critical component of early Alzheimer's disease and is related to cognitive deficits. “We know that people with the complete ApoE4 genes are 10 times more likely to suffer from the most common
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One comment

  1. Ed Martinez says:

    Eureka. Finally out of the amyloid trap. Ever since learning about histones and their proximity to DNA I had a hunch that gene activation by their folding or misfolding could was probable.

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