Scientists Identify Genes That May Impact Alzheimer Patients' Brains
April 17, 2012

Scientists Identify Genes That May Impact Alzheimer Patients’ Brains

Researchers have identified four genes that are associated with decreasing size of the hippocampus, a finding that may have impacts with studying Alzheimer's disease.

The hippocampus is one of the brains regions involved with short and long-term memory processes.  It is also one of the first regions of the brain to exhibit damage from Alzheimer's disease.

A team of over 200 scientists from 100 institutions around the world collaborated to map the human genes that boost or sabotage the brains' resistance to a variety of mental illnesses and Alzheimer's.

Paul Thompson, professor of neurology at the David Geffen School of Medicine at UCLA and a member of the UCLA Laboratory of Neuro Imaging said they searched for two things during the study.

"We hunted for genes that increase your risk for a single disease that your children can inherit," Thompson said in a press release. "We also looked for factors that cause tissue atrophy and reduce brain size, which is a biological marker for hereditary disorders like schizophrenia, bipolar disorder, depression, Alzheimer's disease and dementia."

The team recruited brain-imaging labs around the world to pool their brain scans and genomic data, helping them create "Project Enhancing Neuro Imaging Genetics through Meta-Analysis", or ENIGMA.

The researchers measured the size of the brain and its memory centers in thousands of MRI images from 21,151 healthy people while simultaneously screening their DNA.

"Earlier studies have uncovered risk genes for common diseases, yet it's not always understood how these genes affect the brain," Thompson said in the press release. "This led our team to screen brain scans worldwide for genes that directly harm or protect the brain."

The team was looking for whether any genetic variations correlated to brain size, specifically gene variants that deplete brain tissue.

They found a consistent relationship between subtle shifts in the genetic code and diminished memory centers.  They also found the same genes affected the brain in the same ways in people across diverse populations from Australia, North America and Europe.

"Millions of people carry variations in their DNA that help boost or lower their brains' susceptibility to a vast range of diseases," Thompson said. "Once we identify the gene, we can target it with a drug to reduce the risk of disease. People also can take preventive steps through exercise, diet and mental stimulation to erase the effects of a bad gene."

They identified four genetic loci, including seven genes in or near these loci that appear to determine hippocampal volume.

The results show that if one gene is altered, the hippocampus is the same size as that of a person four to five years older.

The investigators also discovered the genes that explain individual differences in intelligence.  They found a variant in a gene called HMGA2 that affected brain size as well as a person's intelligence.

"This is a really exciting discovery: that a single letter change leads to a bigger brain," said Thompson. "We found fairly unequivocal proof supporting a genetic link to brain function and intelligence."

The research was published in the online edition of Nature Genetics on April 15.