UCLA scientists continue to make advances in Alzheimer’s disease. Their latest breakthrough was published in the March 4 online edition of the Proceedings of the National Academy of Sciences. They noted that they had discovered a new risk gene for Alzheimer’s disease by using a new method of brain imaging called a “connectome scan,” which is a special type of brain scan that maps the strength of the brain’s connections. The findings could lead to new therapies that could halt or slow the progression of the disease.
The researchers screened people’s DNA; then used the “connectosome scan” to visualize the brain’s connections. Alzheimer’s disease, which is the commonest cause of dementia in the elderly, erodes those connections that are essential to support thinking, emotion, and memory. With no known cure, the 20 million Alzheimer’s sufferers worldwide lack an effective treatment, and all people are at risk; the risk of developing Alzheimer's doubles every five years after age 65.
The investigators discovered a common abnormality in the human genetic code that increases one’s risk for Alzheimer’s. To find the gene, they used the new method that screens the brain’s connections, the wiring or circuitry that communicates information in the brain. Switching off these Alzheimer risk genes, first discovered 20 years ago, could stop the disorder in its tracks, or delay its onset by many years.
“We found a change in our genetic code that boosts our risk for Alzheimer’s disease,” explained study senior author Paul Thompson, a UCLA professor of neurology and a member of the UCLA Laboratory of Neuro Imaging. He added, “If you have this variant in your DNA, your brain connections are weaker. As you get older, faulty brain connections increase your risk of dementia.”
The researchers screened the DNA of more than 1,000 individuals to find the common “spelling errors” in the genetic code that might heighten risk for disease later in life. In another first, each person received the “connectome scan” as well; the scan measures water diffusion in the brain, which allows it to map the strength of the brain’s connections. Hundreds of computers, calculating for months, sifted through more than 4,000 brain connections and the entire genetic code, comparing connection patterns in people with different genetic variations. In people whose genetic code differed in one specific gene called SPON1, weaker brain connections were found between brain centers controlling reasoning and emotion. The rogue gene also affects how senile plaques build up in the brain: one of the main causes of Alzheimer’s.
The researchers note that developing new therapeutics for Alzheimer’s is a hot area for pharmaceutical research and that the new study is the first of its kind to use “connectome” scans, which reveal the brain’s circuitry and how information is routed around the brain, to discover risk factors for disease. It combines these connectivity scans with extensive genomic screening, to pinpoint what causes faulty wiring in the brain. Dr. Thompson explained, “Much of your risk for disease is written in your DNA, so the genome is a good place to look for new drug targets,” said Thompson, who founded a research network in 2009, known as Project ENIGMA, to pool brain scans and DNA from 26,000 people worldwide. He added, “If we scan your brain and DNA today, we can discover dangerous genes that will undermine your ability to think and plan, and make you ill in the future. If we find these genes now, there is a better chance of new drugs that can switch them off before you or your family get ill.”
The researchers also found that the SPON1 gene can also be manipulated to develop new treatments for Alzheimer’s disease. When the rogue gene was altered in mice, it led to cognitive improvements and fewer plaques built up in the brain. Alzheimer’s patients show an accumulation of these senile plaques, which are made of a sticky substance called amyloid, which destroys brain cells, causing irreversible memory loss and personality changes.
Screening genomes has led to many new drug targets in the treatment of cancer, heart disease, arthritis, and brain disorders such as epilepsy. However, the UCLA team’s approach, screening genomes and brain scans from the same people, promises a faster and more efficient search. “With a brain scan that takes half an hour and a DNA scan from a saliva sample, we can search your genes for factors that help or harm your brain’s connections,” said Dr. Thompson. He added, “This opens up a new landscape of discovery in medical science.”