UCLA Researchers Find Signs of Alzheimer’s Decades Before Illness Strikes
LOS ANGELES, Calif. – Scientists at UCLA have discovered a new genetic risk factor for Alzheimer’s disease by screening people’s DNA, then using an advanced kind of brain scan to visualize the brain’s connections.
Alzheimer’s disease – the commonest cause of dementia in the elderly – erodes those connections, which we rely on to support thinking, emotion, and memory. With no known cure, the 20 million Alzheimer’s sufferers worldwide lack an effective treatment, and we are all at risk - our risk of developing Alzheimer's doubles every five years after age 65.
The researchers discovered a common abnormality in our genetic code that increases our risk for Alzheimer’s. To find the gene, they used a 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.
The research appears in the March 4th online edition of the Proceedings of the National Academy of Sciences.
“We found a change in our genetic code that boosts our risk for Alzheimer’s disease,” said Paul Thompson, senior author of the study, a UCLA professor of neurology, and a member of the UCLA Laboratory of Neuro Imaging. “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 over a thousand people’s DNA, to find, said Thompson, the common “spelling errors” in the genetic code that might heighten risk for disease later in life. In another first, each person received a “connectome scan” as well–a special type of brain scan that 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 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.
“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. “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.” Developing new therapeutics for Alzheimer’s is a hot area for pharmaceutical research, he said.
The researchers also found that the SPON1 gene can also be manipulated to develop new treatments for the devastating 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 – made of a sticky substance called amyloid – which kills 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. But 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 Thompson. “This opens up a new landscape of discovery in medical science.” For more information, see http:// www.neurology.ucla.edu/