Looking for Biomarkers: Protein signature may warn of impending Alzheimer’s disease

Amounts of certain proteins in the blood could tip off doctors to nascent Alzheimer’s disease in people who don’t yet show clear symptoms of the illness, researchers report.

The beginnings of Alzheimer’s resemble the occasional forgetfulness and slight cognitive loss that come with normal aging, making the disease difficult to diagnose at a point when treatment might be most helpful. Tony Wyss-Coray of Stanford University and his colleagues reasoned that the quantities of certain proteins that carry information between cells might provide a diagnostic marker of Alzheimer’s disease. Earlier research had suggested that protein markers could aid Alzheimer’s diagnosis, but those analyses required tapping into spinal fluid—an invasive procedure (SN: 2/18/06, p. 102). Now, Wyss-Coray and his team have designed a protein test that requires only a blood sample.

To narrow the search, the team focused on 120 known signaling proteins. When the researchers measured concentrations of these proteins in Alzheimer’s patients and healthy people, they detected 18 proteins that turned up in inordinately high or low concentrations in the Alzheimer’s patients.

The scientists then checked amounts of these 18 proteins in blood samples obtained several years earlier from 47 people who had mild cognitive impairments at that time. In the interim, 22 of those people had gone on to develop Alzheimer’s disease.

The telltale signature of the 18 proteins showed up in 20 of the 22 people with Alzheimer’s but not in eight patients who had developed other forms of dementia. Of 17 people who still had only mild cognitive impairment up to 6 years after the blood samples were taken, the Alzheimer’s-linked protein signature ominously appeared in seven.

The findings will appear in the November Nature Medicine.

“This is the first study I know of that looks at a blood-based test” for Alzheimer’s, says Kelvin H. Lee, a biochemical engineer at the Delaware Biotechnology Institute in Newark, Del.

“The lack of precise biomarkers for neurodegenerative diseases such as Parkinson’s or Alzheimer’s is really the critical obstacle in the development of disease-modifying drugs,” says neurologist Clemens R. Scherzer of Harvard Medical School in Boston. Biomarkers that identify people with early Alzheimer’s would enable drug researchers to target the most appropriate individuals when testing new drugs, he says.

Currently, no medications can reverse the brain damage and cognitive losses caused by Alzheimer’s, but some can slow the progression of symptoms (SN: 2/18/06, p. 110). If further research shows that protein signatures can provide accurate diagnoses, “it will be much easier to detect Alzheimer’s disease earlier and treat it to stop the damage from happening,” says Eric M. Blaylock, a neuroscientist at the University of Kentucky in Lexington.

Ultimately, Lee says, doctors might need to combine blood, spinal-fluid, brain-imaging, and psychological tests to get an accurate early diagnosis of Alzheimer’s.