Alzheimer’s disease is the result of progressive deterioration in brain function. The disease usually becomes evident among seniors; however, it can occur among younger individual. Now, a new study found that variations in brain structure that progress to Alzheimer’s disease may be present as early as six months of age. The research could lead to interventions that could slow—or even halt—the progression of this debilitating neurological condition. The findings were published online on November 25 in the journal JAMA Neurology by researchers at Brown University, UCLA, UCSD, the University of Arizona, and King’s College London. According to the Alzheimer’s Association, more than 5 million seniors suffer from Alzheimer’s disease, and it is currently the sixth leading cause of death in the U.S.
With brain imaging studies, the researchers found that infants who carry the apolipoprotein E gene (APOE-E4), which is associated with an increased risk for Alzheimer’s disease, also tend to have differences in brain development compared to infants who do not have the gene. The APOE gene has three different versions (alleles): E2, E3, and E4. The E3 allele is the most common; however, the E4 allele is present in 25% of the U.S. population, and it has long been known to increase the carrier’s for late-onset Alzheimer’s disease. Not everyone who carries the gene develops Alzheimer’s disease; however, 60% of individuals diagnosed with Alzheimer’s carry at least one copy of the E4 gene allele. An individual can carry one or two copies of any given gene because all chromosomes that carry genes are paired.
The E4 allele is believed to underlie several different brain functions; however, at present, the mechanisms behind its involvement in Alzheimer’s disease is unclear. One theory is that it is involved in the maintenance of myelin sheath, which is the insulating layer surrounding the nerves in the brain and spinal cord. Alzheimer’s and other neurodegenerative diseases are known to cause damage to the myelin sheath; therefore, it is possible that people who carry the E4 allele have a reduced ability to repair the myelin sheath. In view of this theory, the researchers proposed that the allele might also be involved in myelin development during infancy.
To test their theory, the investigators conducted brain imaging studies on 162 healthy infants between the ages of 2 months and 25 months. Each infant also had a DNA test done, which revealed that 60 of them carried the E4 gene variant and the others had the E3 variant. The brain scans were conducted using a special magnetic resonance imaging (MRI) technique that had been developed at Brown’s Advanced Baby Imaging Lab. The method involves silencing the MRI scanner as much as possible. This resulted in reducing the mechanical hum to an almost undetectable level; thus, the infants’ brains could be scanned while they slept without the need for medication.
The MRI scans were able to plot the development of the infants’ gray matter, which is the portion of the brain that contains nerves and nerve fibers; it also allowed the investigators to plot the brain’s white matter, which is the insulating layer of the brain that contains the myelin. When the scans were compare, the investigators found profound differences between the brains of infants with the E4 allele and the E3 allele. They found that, during the first 6 months, the myelin sheath was laid down much more rapidly in the E4 carriers, compared to the E3 carriers; in addition, the E4 carriers had more myelin than the E3 carriers. After a year, the E3 carriers caught up with myelin production; however, at 2.5 years, the E3 carries had more myelin than the E4 carriers. Therefore, the E3 carriers laid down myelin later but they developed it faster once it was laid down.
The study authors note that their findings increase understanding of the E4 allele and how it may potentially relate to Alzheimer’s later on in life. At present, both the E3 and E4 carriers are performing similarly in terms of cognitive function and behavior; however, the investigators plan to continue following the babies’ development. The researchers concluded that their findings should be considered preliminary; however, the study demonstrates some of the earliest brain changes associated with the genetic predisposition to Alzheimer’s disease. Thus, it raises new questions about the role of the APOE-E4 allele in normal human brain development, the extent to which these processes are related to subsequent Alzheimer’s disease pathology, and whether it could be targeted by Alzheimer’s prevention therapies.