Blood-based biomarkers may predict cognitive impairment associated with Alzheimer’s disease

Early-stage Alzheimer’s disease, or AD, increasingly is the target of drug development efforts, but there are very few tools that measure the cognitive function of patients with the condition before the onset of dementia. Experts have concluded that it is best to treat patients prior to changes in cognition, before the symptoms of neurodegeneration appear. As a result, scientists have turned to biomarkers to provide some indication of whether AD is likely to develop.

Although cognitive capacity may not be measured easily before AD has caused significant neuronal damage, there now is a simple blood test that may predict whether a healthy person is likely to develop mild cognitive impairment or AD within a two- to three-year time frame with more than 90% accuracy.

The researchers behind the test — led by Howard Federoff, M.D., EVP health sciences at Georgetown University Medical Center — enrolled 525 healthy participants ages 70 years or older into a five-year observational study. Federoff and colleagues determined there were 74 participants who displayed signs of preclinical AD after testing participants for memory performance. Then the researchers compared the blood plasma biomarker levels of 53 of those 74 participants showing signs of cognitive impairment with those of 53 participants who were cognitively healthy.

The researchers determined that a set of 10 phospholipids predicted “phenoconversion” to the cognitive functional impairment that is the hallmark of AD. “This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer’s disease,” Mark Mapstone, M.D., wrote in a letter published in Nature Medicine. 

The lower level of 10 lipids in the blood in the study subjects who went on to develop functional impairment might reflect the breakdown of neural cell membranes, the researchers hypothesized.

There are already tests in existence that measure cognitive function, but these rely on the examination of cerebrospinal fluid or brain imaging scans, and involve testing methods that are considered both expensive and complicated. A test that uses blood samples may be much cheaper and more practical in terms of widespread use, although the study researchers admit that the results need to be validated on a much larger scale for any definitive conclusions to be made.

This begs the question: How will patients change their behavior if they are found to have signs of the biomarkers associated with AD? There are currently no suitable disease-modifying therapies to treat AD, so having the knowledge of a predisposition for the condition may not be quite so helpful. However, knowledge of this risk could allow patients to enroll in experimental clinical trials, and could help scientists better understand the etiology of AD. 

Although beta amyloid has been thought to be a promising therapeutic target for AD, many of the drugs that have been developed with the belief that reducing the amount of amyloid in the brain halts disease progression have failed in clinical trials.