Discovery may show earliest stage of Alzheimer's

A new way to detect Alzheimer’s disease at the earliest stages has been reported in a study led by researchers at the Sanford Burnham Prebys Medical Discovery Institute.

The researchers found a biological molecule, or biomarker, that’s associated with brain inflammation. This is believed to be a trigger for the Alzheimer’s process, which takes many years to produce symptoms.

The expectation is that if further animal work goes well, a study in people could be considered in a couple of years, said Aman Mann, one of the study authors. The technology could be used as a diagnostic or possibly a means of delivering therapies to the brain.

The technology has been licensed to the San Diego biotech startup AivoCode.

The study was published Friday in Nature Communications. Other key authors were Pablo Scodeller and Erkki Ruoslahti, also of SBP.

Alzheimer's disease, the most common cause of dementia, is a progressive brain disease that gradually erodes people's memory, ability to think, communicate and take care of themselves.

Attempts to reverse or slow down Alzheimer’s to date have all failed. Scientists say this is because those treated were already exhibiting symptoms, by which time irreversible brain damage has already occurred. So the researchers decided to look a step earlier in the disease process.

They ​​​​​​identified a protein fragment, or peptide, that indicates brain inflammation and tissue repair in both the mouse models and human patients. It binds to a protein called CTGF that is produced in the brain’s blood vessels when this process takes place.

In the mouse models, CTGF was found in cells that form the inner lining of blood vessels in the parts of the brain affected by Alzheimer’s. Unlike most cells in the brain, these cells are outside a protective membrane called the blood-brain barrier that keeps out most substances.

These two facts mean it could be possible to develop an imaging method that detects the protein, enabling identification of people in which Alzheimer’s has begun, Mann said.

And because the protein is found where the disease takes place, it could also serve as a target for therapies.

Brain inflammation is thought to be important in the development of Alzheimer’s, said Michael Plopper, M.D., Chief Medical Officer of Sharp Behavioral Health Services.

“This finding may create a biomarker for detecting Alzheimer’s disease before the brain has been damaged by the disease process,” Plopper said by email. “Early studies indicate this may hold true for humans as well. These findings may lead to very early detection and also potentially new treatments."

Shelita Weinfield, president of Alzheimer's San Diego, said the study gives hope.

“We are encouraged by the news that an easier way to diagnose Alzheimer's disease could be on the horizon. The earlier Alzheimer's can be detected and diagnosed, the better a family is able to plan for the future. Until the day a cure is found, we are here to provide care and support for local families."

Previously, scientists had thought that deposits of an abnormal protein called beta amyloid triggered the disease, Mann said. While amyloid is involved, the process is now understood to be more complicated.

Changes in the blood vessels in the brain are now believed to precede and enable amyloid accumulation in neurons, Mann said.

“Our thinking was to determine what was happening in the blood vessels of Alzheimer’s brains, and recognizing those changes,” he said.

A previous study had found that high levels of CTGF are produced in the brain of Alzheimer’s patients. But researchers didn’t make the link to production of the protein early on in blood vessels.

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