7th March 2013

Brain scans could detect Alzheimer's decades before illness strikes

By screening people's DNA and then using an advanced type of scan to visualise their brains' connections, scientists at UCLA have discovered a new genetic risk factor for Alzheimer's.

Alzheimer's disease, the most common cause of dementia in the elderly, erodes these connections, which we rely on to support thinking, emotion and memory. With no known cure for the disease, the 20 million Alzheimer's sufferers worldwide lack an effective treatment. And we are all at risk: our chance of developing Alzheimer's will double every five years after the age of 65.

The UCLA researchers discovered a common abnormality in our genetic code that increases the risk of Alzheimer's. To find the gene, they used a new imaging method that screens the brain's connections – the wiring, or circuitry, that communicates information. Switching off such Alzheimer's risk genes (nine have been implicated over the last 20 years) could stop the disorder in its tracks, or delay its onset by many years.

Professor Paul Thompson, senior author of the study: "We found a change in our genetic code that boosts our risk for Alzheimer's disease. 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' work involved screening more than a thousand people's DNA to find the common "spelling errors" in the genetic code that might heighten their risk for the disease later in life. The new study was the first of its kind to also give each person a "connectome scan," a special type of scan that measures water diffusion in the brain, allowing scientists to map the strength of the brain's connections.

The new scan reveals the brain's circuitry and how information is routed around the brain, in order to discover risk factors for disease. The researchers then combined these connectivity scans with the extensive genomic screening to pinpoint what causes faulty wiring in the brain.

SPON1

Hundreds of computers, calculating for months, sifted through over 4,000 brain connections and the entire genetic codes, comparing connection patterns in people with different genetic variations. In people whose genetic code differed in one specific gene called SPON1, weaker connections were discovered between brain centres controlling reasoning and emotion. This rogue gene also affects how senile plaques build up in the brain – one of the hallmarks of Alzheimer's disease.

"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 in 2009 founded a research network 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 will 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. It has also been found that the SPON1 gene can be manipulated to develop new treatments for the devastating disease, Thompson noted. When the rogue gene was altered in mice, it led to cognitive improvements and fewer plaques building up in the brain. Alzheimer's patients show an accumulation of these senile plaques, which are made of a sticky substance called amyloid and are thought to kill brain cells, causing irreversible memory loss and personality changes.

Screening genomes has led to many new drug targets for treatment of cancer, heart disease, arthritis and brain disorders such as epilepsy. But the UCLA team's approach – screening genomes and performing brain scans of 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," Thompson said. "This opens a new landscape of discovery in medical science."

The research was published this week in Proceedings of the National Academy of Sciences.

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