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Gene Variant Linked To Alzheimer’s Might Affect Brain Development In Children

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The gene that raises the risk for Alzheimer’s Disease in adults also affects brain development and mental abilities in children, a new study found.

Researchers examined brain scans of 1,187 children and teenagers, and found distinct patterns in the size and structure of the cortex, hippocampus and other parts of the brain. These patterns have been associated with different variants of the gene APOE, which factors in up to 25% of Alzheimer’s cases, reports the Los Angeles Times.

The researchers, led by Dr. Linda Chang, director of the Neuroscience and MRI Research Program at the University of Hawaii, likewise found a link between the APOE variant each child had and how well they did on tests that measured cognitive function, working memory and attention span.

These findings suggest that Alzheimer’s may be much more than the long-long held theory that the disease is related to the brain’s failure to clear beta amyloid plaque buildup. Instead, it may be wise to consider it a developmental disorder.

The APOE gene directs cells to make the protein apolipoprotein E, which helps form the molecules that ferry cholesterol and other fats throughout the bloodstream. These molecules also carry beta amyloid proteins out of the brain.

The gene has three variants: e2, e3 and e4. Everyone inherits one version of this gene from each parent, making it six combinations that one person might have. Those who have one, and most especially two, e4 variants are more likely to develop Alzheimer’s compared to those who don’t. Previous studies have also found that adults with e2 variants of the gene have more brain plaque but are less at risk for the disorder.

Chang’s team wanted to see if these gene variants affected the brains earlier in life. They tested healthy subjects aged 3 to 20 from across the country and placed them in the Pediatric Imaging, Neurocognition and Genetics Study. The participants gave the scientists saliva samples so their DNA could be sequenced, and took a series of tests that measured different aspects of cognitive function. They also got MRI scans.

The results found a number of differences in mental abilities and brain structure based on how old the participants were and the APOE gene variant they had. The differences stayed the same even after the scientists factored in things like gender, genetic ancestry, parents’ educations and socio-economic status.

Children with the e4/e4, e2/e2 and e2/e4 variations of the APOE gene showed different trajectories in brain development compared to children who had at least one e3 variant. The brain regions affected were the same ones often affected by Alzheimer’s as well, the study said.

The kids who had e2/e4 variants had less volume in the hippocampus, which helps in long-term memory. Also in the hippocampus, children with e4/e4 seemed to have lower myelination, which would block the transmission of signals between neurons. Both of these situations were similar to the brains of elderly people who had the same genetic variants.

The researchers also found that younger children with these two specific variants and different brain development also scored lower on tests for working memory and attention span.

Aside from that, children with e4/e4 variants showed signs of atypical development in the cortex that were similar to those seen in children with fetal alcohol syndrome.

The researchers inferred their results on brain development by comparing children at different ages, since brain development naturally varies from person to person. They added that it is important to track the children individually over a longer period of time.

Dr. M. Elizabeth Ross of Weill Cornell Medical College and Rebecca Knickmeyer of UNC Chapel Hill wrote an op-ed that accompanied the study, saying that the results are “extremely intriguing” and that they “support the provocative idea that AD (Alzheimer’s disease) is, in part, a developmental disorder.”

Ross and Knickmeyer said that if this is so, it is likely that treatments can be developed for children with high-risk APOE variants that would delay the onset of Alzheimer’s when they got older, or even prevent it.

The study was published in the journal Neurology.

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