An Alzheimer-Related Gene?

Neuroscience_Neurology.jpgThe genetic basis for Alzheimer’s disease has been a focus of research in recent years, and the gene most studied so far has been the ApoE gene, which codes for apoprotein E, a blood protein concerned with the transport of lipids in blood. Specifically, ApoE is thought to be associated with the development of atherosclerosis, the laying of fatty plaques inside the walls of our arteries.

Which one of the three versions of the gene we inherit has an important role to play in the development of the entorhinal cortex, part of the undersurface of our forebrain which plays a crucial role in the development of our memory and learning.

A recent study published in in Lancet, based on imaging the brains of 239 children and adolescents with the ApoE4 variant of the gene, confirms that the presence of the gene leads to having a thinner entorhinal cortex, possibly predisposing us to neurodegenerative disorders when we get older, notably Alzheimer’s disease.

Loss of neurons start soon after birth in all of us, but a huge reserve pool ensures that the loss does not reach critical levels that start producing symptomatic loss of brain function. However in genetically predisposed individuals, premature loss of the cell populations might lead to a rapid deterioration in cognitive function once the critical level of cell population is reached, particularly in old age. Although the thinned brain tissue observed in the young participants in the study did not have any effect on their intellectual abilities, the study recommended further follow up studies in healthy adults with the “signature” ApoE4-related cortical thinning to actually confirm the onset of pre-senile loss of intellectual capacity before confirming the association.

Previous studies have shown that 10-25 percent of the population possess the ApoE4 gene, but in up to 40 percent of patients with late-onset Alzheimer’s disease. The ApoE gene is thought to be related to brain cell repair and regeneration, with the ApoE4 variant thought to be related to be somewhat deficient in this capacity. Fortunately, the study reveals that the thinning of the cortex does not progress beyond childhood, and so far has little correlation with intellectual performance in early adulthood. The ApoE2 version is associated with normal cortical thickness, while the relatively rare ApoE3 variant has been linked to intermediate thicknesses of the entorhinal cortex.

But its role as a predisposing factor to late-onset Alzheimer deterioration is based on statistical evidence, and needs further evaluation.


Shaw P, Lerch JP et al. Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study. Lancet Neurology 2007; 6:494-500.

Sudip Ghosh, MD

Sudip Ghosh, MD, is a surgeon at the University of Manchester, UK and a medical writer.
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