Scientists at Scripps Research announced on Mar. 9 the development of a new blood-based test that examines how proteins are folded in the bloodstream, potentially offering earlier detection of Alzheimer's disease. The study, published in Nature Aging on February 27, reports that structural differences in three plasma proteins can distinguish cognitively normal individuals from those with Alzheimer's and mild cognitive impairment with high accuracy.
This research is significant because current tests for Alzheimer's often measure the levels of amyloid beta and phosphorylated tau proteins but may not fully capture earlier biological changes linked to disease progression. By focusing on protein structure rather than concentration, the new approach could enable diagnosis and intervention at an earlier stage.
The team analyzed plasma samples from 520 people across three groups: cognitively normal adults, individuals with mild cognitive impairment, and patients diagnosed with Alzheimer's. Using mass spectrometry and machine-learning algorithms, they found that as Alzheimer's progressed, certain blood proteins became less structurally "open." Three proteins—C1QA (involved in immune signaling), clusterin (associated with protein folding and amyloid clearance), and apolipoprotein B (which helps transport fats)—showed strong correlations with disease state.
"The correlation was amazing," said co-author Casimir Bamberger, a senior scientist at Scripps Research. "It was very surprising to find three lysine sites on three different proteins that correlate so highly with disease state."
The model classified individuals as cognitively normal, having mild cognitive impairment or Alzheimer's with approximately 83% overall accuracy. In some comparisons, such as distinguishing healthy individuals from those with mild cognitive impairment, accuracy exceeded 93%. The test also performed consistently across independent cohorts and follow-up samples months later.
Yates said, "Detecting markers of Alzheimer's early is absolutely critical to developing effective therapeutics. If treatment can start before significant damage has been done, it may be possible to better preserve long-term memory."
While promising, researchers note that larger validation studies are needed before the test is ready for clinical use. They are also exploring whether this structural profiling approach could be applied to other diseases such as Parkinson's and cancer.
