Side effects of Alzheimer's gene visible in child brain development

Certain genes increase the risk of developing Alzheimer’s disease. The side effects of the most common of these genes, apolipoprotein E, may be evident as early as in childhood, a study finds.
[Illustration of brain and genes]
Studying genes in childhood that increase the risk of developing Alzheimer’s disease may possibly help experts develop ways of delaying the disease.

Genetic risks are just one of the factors that may increase or decrease a person’s chances of developing Alzheimer’s disease (AD), along with age and family history.

While the symptoms of the rarer early-onset AD – representing less than 5 percent of people with the disease – can appear from the age of 30, the symptoms of the more common type, late-onset AD, is apparent over the age of 65.

This study, published in the online issue of Neurology, finds that the effects of the AD gene apolipoprotein E (APOE) may possibly be seen before the age of 20.

The APOE gene, located on chromosome 19, is the gene that has the greatest known influence on the risk of developing late-onset AD. Everyone carries two copies of the APOE gene, one inherited from each parent, and there are three common forms – or alleles – of APOE, including:

  • APOE ε2 – the least common form that may provide mild protection against AD
  • APOE ε3 – the most common form that appears to have no effect on the risk of the disease
  • APOE ε4 – increases the lifetime risk of developing AD by up to four times with one copy of the APOE ε4 gene and by 10 times with two copies.

‘Studying genes in children could help find way to prevent disease’

There are six possible APOE gene variants: ε2ε2, ε3ε3, ε4ε4, ε2ε3, ε2ε4, and ε3ε4. Previous studies have shown that people with the ε4 variant of the gene are more likely to develop AD than those with the ε2 and ε3 variants. It is estimated that the ε4 variant may be a factor in 20-25 percent of AD cases.

“Studying these genes in young children may ultimately give us early indications of who may be at risk for dementia in the future and possibly even help us develop ways to prevent the disease from occurring or to delay the start of the disease.”

Linda Chang, MD, study author, University of Hawaii in Honolulu

The study included 1,187 children aged between 3-20 years who had no brain disorders or issues that would affect their brain development. The children underwent brain scans, genetic testing, and were tested on their thinking and memory skills.

APOE ε4 is present in around 10-15 percent of the population. When compared with children with the ε2 and ε3 gene variant, those children in the study with the ε4 gene had differences in brain development in the areas of the brain that are often affected by AD.

The hippocampus – the area of the brain that helps regulate emotion, learning, and memory – was almost 5 percent smaller in children with the ε2ε4 genotype, than the hippocampi in the children with the ε3ε3 genotype.

Children with certain genotypes had lower memory and thinking skills

Children in the study who inherited two copies of the ε4 alleles (ε4ε4) scored lower on a brain scan that displays the structural integrity of the hippocampus.

“These findings mirror the smaller volumes and steeper decline of the hippocampus volume in the elderly who have the ε4 gene,” says Chang.

Chang and team found that scores on memory and thinking skills were low in children with the ε4ε4 or ε4ε2 genotype.

The youngest of the children with the ε4ε4 genotype scored up to 50 percent lower on executive function and working memory tests, and some of the youngest with the ε2ε4 genotype scored up to 50 percent lower on attention tests.

The results also showed that those children over the age of 8 with the ε4ε4 and ε2ε4 genotypes had results and test scores that were comparable to other children.

While this study is promising in identifying who could be at risk of AD from an early age, the study has some limitations. The data for each child was from one point in time, and the age groups for the less common ε4ε4 and ε2ε4 variants had fewer participants than the more common gene variants.

Read about a genetic risk score that may identify adults who are at risk of Alzheimer’s disease.

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