Early Alzheimer’s detection key to treatment

Sometime in the near future, probably in our lifetime, a patient will be able to undergo a test that will identify the biological markers of Alzheimer’s disease, much like cholesterol now serves as a biomarker for heart disease. Treatment will come in the form of a vaccine.

Such developments will be a huge breakthrough for a disease that today has no cure and can only be definitely diagnosed after death, when a patient’s brain is autopsied.

“A ton of work is being done in the field,” says Dr. Maria Carrillo, director of medical and scientific relations for the Alzheimer’s Association. “We are on the hunt for early detection tests that can be done in a general practitioner’s office.

“And as far as medicines are concerned, we’re looking at a very robust pipeline.”

Alzheimer’s, the most common form of dementia, afflicts as many as 5.2 million Americans. And as the population ages, the Alzheimer’s Association expects half a million new cases a year, with 10 million baby boomers eventually developing the fatal degenerative disease.

Mass marketing a test to identify the disease before patients develop clinical symptoms means that therapies, including drugs, may be able to stop the progression and preserve normal functions.

“I can’t stress enough the importance of diagnosing early,” says Dr. Richard Isaacson, director of the Alzheimer’s Division at the University of Miami at the Leonard M. Miller School of Medicine. “The earlier we find out, the better the patient will do.”

Isaacson and his staff recently launched a clinical trial looking at an amino acid, BMAA, in hair samples of Alzheimer patients and a control group. They are hoping to determine if the presence of this amino acid is predictive of the disease, or a result of the degenerative process itself.

There is also hopeful talk of a vaccine.

“In the vaccine trials, we are asking: Are there ways to immunize people to prevent accumulation of amyloid plaque?” says Dr. Ralph Sacco, chairman of University of Miami’s Department of Neurology. “How much of memory loss is preventable?”

Tests

Here are some of the more promising trials for diagnostic testing and therapy:

•Blood tests: While researchers in numerous labs are focusing on predictive blood screening tests, the Alzheimer’s Association singles out one that is farther along in clinical research trials. It targets lymphocytes, or white blood cells.

The test measures CD-69, a protein involved in white blood cell growth and production and was accurate 91 percent of the time in identifying Alzheimer’s patients, regardless of severity – making it a possibility for detection during the early stages of Alzheimer’s.

•Positron emission tomography (PET scans): Presently, a PET scan can create images of harmful beta amyloid plaque in the brains of living Alzheimer patients, but the dye used in the scan doesn’t last long.

Since half of its radioactivity is lost every 20 minutes, it must be manufactured onsite. This in turn requires a cyclotron machine rarely found in community hospitals. These constraints limit accessibility.

Recently however, researchers have developed a new radioactive agent that can be injected into patients to be scanned. This agent, 18F-AV-45, is longer lasting and allows high-quality images to be taken for longer periods of time.

•Spinal fluid. Researchers from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a comprehensive project that helps researchers and clinicians develop treatments and monitor their effectiveness, have developed a test to help diagnose the early stages of Alzheimer’s sooner and more accurately by measuring two biomarkers – tau and beta-amyloid proteins – in cerebrospinal fluid.

Amyloid is the dangerous brain plaque found in Alzheimer’s patients, and tau forms tangles within cells and may prevent neurons from communicating with each other.

Separately, researchers at Mt. Sinai Medical Center in Miami Beach, Fla., have developed a software program that radiologists can use with an MRI to visually rate the severity of a patient’s medial temporal lobe atrophy.

The ratings are useful in predicting whether a person with mild cognitive impairment will develop Alzheimer’s. The use of this software might lead to more accurate diagnosis of the disease at a very early stage.

Therapy

Much of the research into therapies focuses on anti-amyloid therapy. Scientists believe that this microscopic protein interrupts cell-to-cell communication, prompts immune cells to trigger inflammation and eventually kills cells. It is not known if the protein is a cause or result of Alzheimer’s.

One drug in early trials is being tested for its ability to inhibit formation of clusters of this brain-clogging plaque.

Researchers also have been experimenting with an active vaccine, ACC-001, that prompts the body to produce antibodies to attack beta-amyloid.

Others are experimenting with passive vaccines designed to directly remove beta-amyloid from the brain. The most promising, AAB-001, has been given a fast-track designation by the U.S. Food and Drug Administration.

Other research has linked a high intake of omega-3s – a type of polyunsaturated fatty acid normally associated with heart health – to a possible reduction in risk of dementia or cognitive decline.

“There are so many people working on this that I don’t see it not coming to fruition,” says Chad Dickey, assistant professor in the department of molecular medicine at the University of South Florida.

In the meantime, as this research makes its way to market, scientists say exercising four or five times a week and keeping socially and intellectually active are still the best ways to slow the progression of the disease.

“Physical exercise is an absolute essential,” Isaacson says. “But beyond that, keep mentally active. Learn new things.

“We don’t have any magic bullet, but there are good therapies out there. Patients can have hope.”