Conference Coverage

New blood test may detect preclinical Alzheimer’s years in advance


 

FROM CTAD21

A new blood test that identifies a variant of the protein P53 appears to predict Alzheimer’s disease (AD) progression up to 6 years in advance of a clinical diagnosis, early research suggests.

Analysis of two studies showed the test (AlzoSure Predict), which uses less than 1 ml of blood, had numerous benefits compared with other blood tests that track AD pathology.

“We believe this has the potential to radically improve early stratification and identification of patients for trials 6 years in advance of a diagnosis, which can potentially enable more rapid and efficient approvals of therapies,” Paul Kinnon, CEO of Diadem, the test’s manufacturer, said in an interview.

The findings were presented at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference.

Positive “discovery” results

P53, which is present in both the brain and elsewhere in the body, “is one of the most targeted proteins” for drug development in cancer and other conditions, said Mr. Kinnon.

The current blood test measures a derivative of P53 (U-p53AZ). Previous research suggests this derivative, which affects amyloid and oxidative stress, is also implicated in AD pathogenesis.

Researchers used blood samples from patients aged 60 years and older from the Australia Imaging, Biomarkers, and Lifestyles (AIBL) study who had various levels of cognitive function.

They analyzed samples at multiple timepoints over a 10-year period, “so we know when the marker is most accurate at predicting decline,” Mr. Kinnon said.

The first of two studies was considered a “discovery” study and included blood samples from 224 patients.

Results showed the test predicted decline from mild cognitive impairment (MCI) to AD at the end of 6 years, with an area under the curve (AUC) greater than 90%.

These results are “massive,” said Mr. Kinnon. “It’s the most accurate test I’ve seen anywhere for predicting decline of a patient.”

The test can also accurately classify a patient’s stage of cognition, he added. “Not only does it allow us to predict 6 years in advance, it also tells us if the patient has SMC [subjective memory complaints], MCI, or AD with a 95% certainty,” Mr. Kinnon said.

He noted that test sensitivity was higher than results found from traditional methods that are currently being used. The positive predictive value (PPV) and negative predictive value (NPV), which were at 90% or more, were “absolutely fantastic,” said Mr. Kinnon.

“Better than expected” results

In the second “validation” study, investigators examined samples from a completely different group of 482 patients. The “very compelling” results showed AUCs over 90%, PPVs over 90%, and “very high” NPVs, Mr. Kinnon said.

“These are great data, better than we expected,” he added.

However, he noted the test is “very specific” for decline to AD and not to other dementias.

In addition, Mr. Kinnon noted the test does not monitor levels of amyloid beta or tau, which accumulate at a later stage of AD. “Amyloid and tau tell you you’ve got it. We’re there way before those concentrations become detectable,” he said.

Identifying patients who will progress to AD years before they have symptoms gives them time to make medical decisions. These patients may also try treatments at an earlier stage of the disease, when these therapies are most likely to be helpful, said Mr. Kinnon.

In addition, using the test could speed up the approval of prospective drug treatments for AD. Currently, pharmaceutical companies enroll thousands of patients into a clinical study “and they don’t know which ones will have AD,” Mr. Kinnon noted.

“This test tells you these are the ones who are going to progress and should go into the study, and these are the ones that aren’t. So it makes the studies statistically relevant and accurate,” he said.

Investigators can also use the test to monitor patients during a study instead of relying on expensive PET scans and painful and costly spinal fluid taps, he added.

Previous surveys and market research have shown that neurologists and general practitioners “want a blood test to screen patients early, to help educate and inform patients,” said Mr. Kinnon.

Further results that will include biobank data on more than 1,000 patients in the United States and Europe are due for completion toward the end of this year.

The company is currently in negotiations to bring the product to North America, Europe, and elsewhere. “Our goal is to have it on the market by the middle of next year in multiple regions,” Mr. Kinnon said.

Encouraging, preliminary

Commenting on the findings, Percy Griffin, PhD, MSc, director of scientific engagement at the Alzheimer’s Association, said “it’s exciting” to see development of novel ways for detecting or predicting AD.

“There is an urgent need for simple, inexpensive, noninvasive, and accessible early detection tools for Alzheimer’s, such as a blood test,” he said.

However, Dr. Griffin cautioned the test is still in the early stages of development and has not been tested extensively in large, diverse clinical trials.

In addition, although the test predicts whether a person will progress, it does not predict when the person will progress, he added.

“These preliminary results are encouraging, but further validation is needed before this test can be implemented widely,” he said.

Technologies that facilitate the early detection and intervention before significant loss of brain cells from AD “would be game-changing” for individuals, families, and the healthcare system, Dr. Griffin concluded.

A version of this article first appeared on Medscape.com.

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