Risk genes for Alzheimer’s and mental illness linked to brain changes at birth

Some brain changes that are found in adults with common gene variants linked to disorders such as Alzheimer’s disease, schizophrenia, and autism can also be seen in the brain scans of newborns.

“These results suggest that prenatal brain development may be a very important influence on psychiatric risk later in life,” said Rebecca C. Knickmeyer, PhD, lead author of the study and assistant professor of psychiatry in the University of North Carolina School of Medicine. The study was published by the journal Cerebral Cortex on Jan. 3, 2013.

The study included 272 infants who received MRI scans at UNC Hospitals shortly after birth. The DNA of each was tested for 10 common variations in 7 genes that have been linked to brain structure in adults. These genes have also been implicated in conditions such as schizophrenia, bipolar disorder, autism, Alzheimer’s disease, anxiety disorders and depression.

For some polymorphisms – such as a variation in the APOE gene which is associated with Alzheimer’s disease – the brain changes in infants looked very similar to brain changes found in adults with the same variants, Knickmeyer said. “This could stimulate an exciting new line of research focused on preventing onset of illness through very early intervention in at-risk individuals.”

But this was not true for every polymorphism included in the study, said John H. Gilmore, MD, senior author of the study and Thad & Alice Eure Distinguished Professor and Vice Chair for Research and Scientific Affairs in the UNC Department of Psychiatry.

For example, the study included two variants in the DISC1 gene. For one of these variants, known as rs821616, the infant brains looked very similar to the brains of adults with this variant. But there was no such similarity between infant brains and adult brains for the other variant, rs6675281.

Several genes have been associated with Alzheimer’s disease, but more research is needed.

Alzheimer’s genes are genes that make you more likely to develop Alzheimer’s disease. Genes control the function of every cell in your body. Some genes determine basic characteristics, such as the color of your eyes and hair. Other genes can make you more likely to develop certain diseases - including Alzheimer’s.

Researchers have identified several Alzheimer’s genes - genes that are associated with Alzheimer’s disease. But genetic risk factors are just one part of the Alzheimer’s story, a complex narrative that scientists continue to try to unravel.

“This suggests that the brain changes associated with this gene variant aren’t present at birth but develop later in life, perhaps during puberty,” Gilmore said.

“It’s fascinating that different variants in the same gene have such unique effects in terms of when they affect brain development,” said Knickmeyer.

Most common late-onset Alzheimer’s gene

While some rare forms of Alzheimer’s occur before the age of 65, the most common variety of Alzheimer’s usually begins after the age of 65. The most common gene associated with this late-onset Alzheimer’s is called apolipoprotein E (APOE).

APOE has three common forms:

  APOE e2 - the least common - appears to reduce the risk of Alzheimer’s.
  APOE e4 - a little more common - appears to increase the risk of Alzheimer’s.
  APOE e3 - the most common - doesn’t seem to affect the risk of Alzheimer’s in either direction.

Genes aren’t only factor
Because you inherit one APOE gene from your mother and another from your father, you have two copies of APOE gene - for example, one APOE e3 gene and one APOE e4 gene. Having at least one APOE e4 gene increases your risk of developing Alzheimer’s. And if you have two APOE e4 genes, your risk is even higher.

But not everyone who has an APOE e4 gene - or even two APOE e4 genes - develops Alzheimer’s. And the disease occurs in many people who have no APOE e4 gene. This indicates that the APOE e4 gene affects risk, but it is not a causative gene. Other genetic and environmental factors are likely involved in the development of Alzheimer’s.


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