Blood-Based Biomarkers Seen as Breakthrough for Early Diagnosis and Treatment of Alzheimer’s Disease

Martha Snyder Taggart, BrightFocus Editor, Science Communications
  • Science News
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Six vials of blood.

On March 9, the journal Nature Medicine reported progress towards a blood test for preclinical Alzheimer’s disease (AD). The authors of a new study say they have identified blood-based biomarkers that that can predict with > 90% accuracy whether a healthy person will develop mild cognitive impairment (MCI) or Alzheimer’s disease (AD) within three years.

A clinical test based on these findings, if developed, would still be years off. Nonetheless, the article, by Mark Mapstone et al, represents the first known report of blood-based biomarkers for preclinical AD. The research team identified 10 lipids, or fats, that predict disease onset by revealing the breakdown of neural cell membranes. They called their test equal to or greater in accuracy than results obtained from cerebrospinal fluid (CSF) sampling, with the added benefit that blood is easier and less costly to sample—and considerably less painful for patients--than CSF fluid. The study ruled out the APOE4 gene as a significant predictive factor.

The discovery came midway through a five-year Georgetown Medical Center study enrolling 525 healthy participants aged 70 and older whose blood was tested on entry and at various points throughout. Over five years, 74 participants met the criteria for either mild AD or a condition known as amnestic mild cognitive impairment (aMCI), in which memory loss is prominent.

The study’s third year included a lipid biomarker discovery phase matching 53 participants with cognitively normal controls. In that phase, the lipid panel was identified, validated, and found capable of distinguishing with 90% or better accuracy both cognitively normal participants who would progress to MCI or AD within two to three years, as well as those who would remain normal.

An author, Howard J. Federoff, MD, PhD, of Georgetown Medical Center, called the results, “a major step toward the commercialization of a preclinical disease biomarker test,” adding there are plans to launch a clinical trial within two years. 

Why is this study important?

Effective intervention for AD needs to start earlier than is now possible using traditional diagnostic criteria. Clinical investigations of new treatment therapies have disappointed, possibly due in part to the fact that they treated the disease in more advanced stages. This led the National Institute on Aging and Alzheimer’s Association to issue a joint recommendation calling for research into biomarkers of preclinical AD (Sperling RA et al. Alzheimers Dement 2011; 7:280-92). These study results are based on only 53 patient samples, and need to be validated in larger studies of more diverse patient groups. Nonetheless, they are an important step towards development of clinically useful biomarkers for AD.

BrightFocus Perspective

These findings represent important progress on the research horizon. As noted above, biomarkers to detect preclinical AD will help advance research into the development of disease-modifying or preventive early therapies. There may also be debate over screening for AD--and patient views on early diagnostic testing have to be weighed. Not all people want to know in advance whether or not they will develop AD; nor will all people benefit from knowing unless safeguards are in place to ensure their privacy and care following diagnosis.

Glossary Terms

  • Mild cognitive impairment (MCI)  is a condition between normal age-related memory loss and dementia. Individuals with MCI have persistent memory problems (for example, difficulty remembering names and following conversations and marked forgetfulness) but are able to perform routine activities without more than usual assistance. Individuals with MCI are at risk of developing Alzheimer's disease or other forms of dementia.

  • A gene called Apolipoprotein E (ApoE) appears to be a risk factor for the late-onset form of AD. There are three forms of this gene: ApoE2, ApoE3 and ApoE4. Roughly one in four Americans has ApoE4 and one in twenty has ApoE2. While inheritance of ApoE4 increases the risk of developing AD, ApoE2 substantially protects against the disease.

  • Cerebrospinal fluid (CSF) collection is a test to examine the fluid that surrounds the brain and spinal cord. Scientists are measuring proteins in the CSF to see if they can predict if someone will develop Alzheimer’s disease years before the first symptoms appear.