Indian-American Sandip Ray Leads Alzheimers Breakthrough By Francis C. Assisi (Special to INDOlink)

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In their article titled “classification and prediction of clinical Alzheimer diagnosis based on plasma signaling proteins” Ray and colleagues claimed that they have discovered proteins in blood that can be used to identify Alzheimer's “with close to 90% accuracy and to identify patients who had mild cognitive impairment that progressed to Alzheimer's disease 2–6 years later.”

At the time the work was done, Ray was an employee of Satoris Inc., a San Francisco company co-founded by Ray, Wyss-Coray and Yuen So, MD, PhD, professor of neurology and neurological sciences. Ray and senior author Wyss-Coray are working to commercialize the technology based on their patent “Methods For Diagnosis, Stratification, And Monitoring Of Alzheimer`s Disease.”

According to the patent of Ray and Wyss-Coray, the inventors have discovered “a collection of proteinaceous biomarkers ("AD biomarkers) which can be measured in peripheral biological fluid samples to aid in the diagnosis of neurodegenerative disorders, particularly Alzheimer's disease and mild cognitive impairment (MCI). The invention further provides methods of identifying candidate agents for the treatment of Alzheimer's disease by testing prospective agents for activity in modulating AD biomarker levels.”

IDENTIFYING ALZHEIMERS

Not knowing whether those memory lapses are just that, or the beginning of Alzheimer's disease, is one of the most distressing aspects of the disease, say the researchers who are mostly from the Stanford University School of Medicine.

There are some proteins in blood plasma which cells utilize to pass messages to one another - this blood test identifies changes in these proteins. The scientists have found a link between a change in the cells' dialog and alterations in the brain that comes with Alzheimer's. The researchers explain the blood test indicated who had Alzheimer's disease with 90% agreement with clinical diagnoses. The test could predict onset of the disease 2 to 6 years before symptoms started to become evident.

They claim that biological analysis of the proteins points to “systemic dysregulation of hematopoiesis, immune responses, apoptosis and neuronal support in presymptomatic Alzheimer's disease.”

Senior author, Wyss-Coray, wrote "Just as a psychiatrist can conclude a lot of things by listening to the words of a patient, so by 'listening' to different proteins we are measuring whether something is going wrong in the cells. It's not that the cells are using new words when something goes wrong. It's just that some words are much stronger and some are much weaker; the chatter has a different tone."

Lennart Mucke, MD, director and senior investigator, Gladstone Institute of Neurological Disease, University of California-San Francisco, who did not take part in the study, said "I really think it has enormous potential. Most researchers in this field agree that there is an urgent need for better lab tests for Alzheimer's disease, and this study has addressed this need admirably."

The researchers explained that listening to cells' messages may also lead to discoveries about other disorders.

Alzheimer's diagnosis today is reached by a process of elimination - the patient is tested for stroke, tumors, alcoholism and other possible causes of memory loss and cognitive decline. These conditions are eliminated until all that is left is Alzheimer's. Alzheimer's is the most common cause of dementia. Currently, the only way diagnosis can be confirmed is by carrying out an autopsy after the patient has died.

There are currently over 5 million Americans with Alzheimer's disease, according to the Alzheimer's Association.

The idea of a blood-test was born when Ray and Wyss-Coray worked together to measure levels of 120 different proteins that cells use to communicate. They wanted to find out whether any of them could be indicators for Alzheimer's.

Ray compared blood samples of five Alzheimer's patients with five samples from healthy people (who did not have the disease). He noticed that there were significant difference in the levels of some proteins which are used for communication between the two groups.

Markus Britschgi, PhD, a postdoctoral scholar in Wyss-Coray's lab, said "This study made me realize that we should get away from this image of a brain isolated from the body. The brain is part of the body and so it's connected in one huge network."

Britschgi managed to obtain 258 archived blood samples from the USA, Sweden, Italy, and Poland, of individuals who had symptoms ranging from nothing abnormal to mild cognitive impairment to advanced Alzheimer's. They tested 120 communication proteins, checking to see whether there were any differences in blood samples of Alzheimer's patients and individuals without the disease. They eventually managed to identify an Alzheimer's-specific pattern with just 18 proteins. The blood test was 90% accurate with 92 individuals who ranged from no symptoms at all to full dementia.

They then tried to predict the development of Alzheimer's with 47 individuals who had mild cognitive impairment and had been monitored from 2 to 6 years. The blood test had been carried out on these individuals several years earlier. The blood test flagged 91% of the people who developed Alzheimer's by the end of the monitoring period (as diagnosed by conventional methods).

Britschgi said "Already we have people approaching us at meetings asking if they can give us a vial of their grandfather's blood for testing."

Even though it appears that this blood test seems to be able to predict Alzheimer's disease, as well as diagnosing it, the scientists stress that tests need to be carried out in other labs to confirm this.

Wyss-Coray said "Our hypothesis is that there is something wrong with the production of certain blood cells, which may be needed to clear that stuff that accumulates in the brain in Alzheimer's disease. That makes a lot of sense, and it is very exciting to think of immune cells and molecules interacting with the brain."

Currently, the clinical diagnosis for Alzheimer's is one of exclusion - by testing for other causes of memory loss and cognitive declines, such as stroke, tumors and alcoholism. If those conditions are eliminated as causes of memory loss, what remains is Alzheimer's, which is the most common cause of dementia. Even the clinical diagnosis is imperfect, and the only definitive diagnosis is by brain autopsy after a person has died.

This breakthrough promises to change that and will be extremely useful as patients can be treated sooner and it can also determine if and how new treatments are having the required effect.

ALZHEIMERS BURDEN

Alzheimer’s Disease carries a tremendous financial and social impact. In the US alone, there are 4-5 million cases identified and >$100 billion dollars spent per year. Currently there is no simple test for Alzheimer’s, and it is estimated that only 61% of Alzheimer's cases in the U.S. are diagnosed.

When Alzheimer’s is diagnosed, several studies have shown that even present therapies, such as Aricept (Pfizer), slow down the progression of debilitating symptoms. This delays entrance into nursing homes, which is by far the largest cost associated with Alzheimer's disease.

Since the destructive neurodegeneration from Alzheimer's may exist years before any symptoms are apparent, much damage can occur prior to diagnosis. With the reliance on clinical criteria and the need for exclusion of other causes of dementia, the current approach to Alzheimer's diagnosis is time and labor intensive, costly, and largely dependent on the expertise of the examiner.

The simple, reliable, non-invasive Satoris test makes use of biological markers that correlate strongly with pathological and clinical signs of the disease, and precede the appearance of clinical symptoms.

A spokesperson for Satoris said: “Our vision is to combine early diagnosis of Alzheimer’s with presently available therapies, a form of predictive medicine. Ultimately, this will lead to the development and use of more effective therapies to slow the progression of the disease or improve existing symptoms, reducing overall healthcare costs.”

“Satoris is poised to enable early detection of this devastating disease, which we hope will both accelerate the development of better medicines and assist physicians in patient diagnosis,” said Patrick Lynn, president and CEO of Satoris. “Our vision is to combine early diagnosis with early treatment, sparing patients the worst effects of Alzheimer’s disease.”

There is no cure for Alzheimer’s, a degenerative brain disease that affects 4.5 million Americans. Experts predict the toll may more than triple by 2050 as the population grays. Since its destructive effects may exist years before symptoms are apparent, much damage can occur prior to diagnosis.

Alzheimer’s diagnosis is costly, and largely dependent on the expertise of the physician. As a result, it is estimated that only 60 percent of cases are diagnosed, leaving 1.8 million undiagnosed patients. Autopsy is the only way to conduct a definitive diagnosis for the disease.

“The early diagnosis of Alzheimer’s disease would be greatly improved by the discovery of biological markers that correlate strongly with pathological and clinical signs of the disease, and precede the appearance of clinical symptoms,” said Todd Golde, M.D., Ph.D., professor, chair of the department of neuroscience at the Mayo Clinic, Jacksonville. “This blood test, if replicated in larger studies, is a major discovery that may lead to more effective therapies to slow the disease’s progression or improve existing symptoms, reducing overall healthcare costs.”