Significant advancements in brain scanning techniques and biological markers are allowing scientists to track the progression of Alzheimer’s disease earlier and with greater accuracy, marking a new era in the development of drugs that could halt or potentially prevent the disease.
“The whole field of Alzheimer’s research is moving in this direction of trying to use imaging methods and biomarkers to establish where people are and then to evaluate how drugs work,” said Greg Cole, a professor of medicine and neurology and associate director of the UCLA Alzheimer’s Disease Research Center.
Alzheimer’s disease results in the substantial loss of neurons, or brain cells, and because of the complexity of the brain, it is difficult to make repairs. It is best to prevent the disease ““ preferably before symptoms appear, Cole said.
“It literally robs people of their minds,” said Gary Small, a professor of psychiatry and biobehavioral sciences at the UCLA Semel Institute for Neuroscience and Human Behavior and the director of the UCLA Center on Aging. “They lose their memory ability, are unable to use language properly, and get to the point where they don’t recognize close family members and friends.”
Alzheimer’s disease is a progressive neurodegenerative condition that is characterized by a buildup of abnormal protein deposits known as plaques and tangles, which accumulate in areas of the brain that control memory, Small said.
The definitive diagnosis of Alzheimer’s disease is made after a patient dies when an autopsy is performed and the brain is stained with special chemical markers, but what Small and his team created is a chemical compound known as FDDNP that could be used in living subjects, he said.
“What’s different (from other staining methods) is that (FDDNP’s) very small, and it’s safe for very small amounts to be injected into the veins of research subjects,” Small said.
Using a PET scanner, a brain imaging device, Small and his team found that there were high concentrations of FDDNP in areas of the brain where large amounts of plaques and tangles are known to be found during autopsies of Alzheimer’s patients. In their study, the marker was found to be more discriminating than other brain imaging techniques such as MRI or PET with a conventional tracer, he said.
Small and other scientists have focused their research on an early stage of the disease known as mild cognitive impairment, or MCI. The stage is characterized by impaired memory without injury in other parts of the brain. It can be thought of as an early symptom of Alzheimer’s disease, said James Lah, associate professor of neurology at Emory University and director of the Emory Cognitive Neurology program
“There are other chemical markers that are thought to give you a measure of plaques, but no other one seems to give a measure of tangles,” Small said. “Tangles build up early on in MCI. This gives you a full picture of (this stage) years before people have symptoms.”
Scientists have also recently identified a receptor in the brain known as LR11 that correlates with cognitive ability.
“The speculation is that the loss of LR11 in a subgroup of MCI individuals may identify those who would have gone on to develop Alzheimer’s versus those who would not have,” Lah said.
Lah and his team found that individuals with Alzheimer’s disease had consistently lower levels of LR11 than normal controls. Subjects with MCI were found to have levels of the receptor intermediate between those with Alzheimer’s disease and the controls and were clustered into two groups: One group had higher levels more similar to controls, while the other group had lower receptor levels similar to Alzheimer’s subjects.
LR11 interacts with a protein that affects the production of the small molecules that accumulate to form plaques in the brains of Alzheimer’s patients.
“It’s an important finding because it indicates that LR11 may be lost in the (pre-symptom) stage (of Alzheimer’s disease),” Lah said.
The research on FDDNP and LR11, along with other recent advancements, may mark a new era in drug discovery for early intervention in Alzheimer’s disease. The LR11 research provides a possible therapeutic target for researchers. If drugs can be used to increase the level of the receptor in the brain or to modulate its function, then they may be able to protect against development of the disease.
The new FDDNP-PET scan technique would allow researchers to evaluate drugs with greater accuracy. Drug companies and research institutions would be able to cut costs and possibly test drugs that are more innovative or test drugs in combination, Cole said.
“It’s a very important advance and has certainly been a major focal point for the Alzheimer’s community in the last several years,” Lah said.