New Blood Test Shows Promise for Early Alzheimer’s Detection

A new blood test developed by researchers at Scripps Research is demonstrating significant accuracy in identifying individuals with Alzheimer’s disease and mild cognitive impairment (MCI), potentially offering a less invasive and more accessible method for early diagnosis. The test focuses on structural changes in proteins within the blood, rather than simply measuring their concentrations, representing a shift in Alzheimer’s diagnostic approaches.

The Challenge of Early Alzheimer’s Diagnosis

Currently, diagnosing Alzheimer’s disease often relies on assessing amyloid beta (Aβ) and phosphorylated tau (p-tau) levels in cerebrospinal fluid or through expensive and sometimes invasive brain imaging. Although, these methods may not always capture the earliest biological changes associated with the disease. According to the Spanish Society of Neurology, there are approximately 800,000 people with Alzheimer’s in Spain, highlighting the urgent need for improved diagnostic tools.

How the New Blood Test Works

The Scripps Research team utilized a novel approach involving mass spectrometry to analyze plasma samples from 520 participants across three groups: cognitively normal adults, individuals with MCI, and patients diagnosed with Alzheimer’s. This technique allowed them to measure the degree of exposure or masking of specific protein sites – an indicator of structural change – and identify patterns associated with disease stage using machine learning algorithms. The research, published in Advanced Science on May 21, 2024, revealed that as Alzheimer’s progressed, certain blood proteins became less structurally “open.”

Key Proteins Identified

Three proteins stood out as particularly informative biomarkers:

• C1QA: Involved in immune signaling.
• Clusterin: Associated with protein folding and amyloid clearance.
• Apolipoprotein B: Plays a role in fat transport and blood vessel health.

“The correlation was striking,” says co-author Casimir Bamberger, a senior scientist at Scripps Research. “It was particularly surprising to find three lysine sites on three different proteins that correlate so closely with disease status.”

Accuracy and Performance

The three-marker model demonstrated an overall accuracy of approximately 83% in classifying individuals into the three groups. In direct comparisons, such as distinguishing between healthy individuals and those with MCI, the accuracy exceeded 93%. The test maintained its accuracy when tested on repeat blood samples collected months apart, classifying disease status with approximately 86% accuracy and reflecting changes in diagnostic status over time. The structural score correlated strongly with cognitive test scores and, to a lesser extent, with MRI measurements of brain atrophy.

Implications for Alzheimer’s Treatment

Researchers believe this new blood test could complement existing tests for amyloid and tau, providing a more comprehensive assessment of disease stage and progression. “Detecting Alzheimer’s markers early is essential to developing effective therapies,” says John Yates, a professor at Scripps Research. “If treatment can be started before significant damage occurs, it may be possible to better preserve long-term memory.”

Future Directions

Whereas promising, the new blood test requires further validation through larger studies with longer follow-up periods before it can be implemented for clinical use. The Scripps Research team is as well investigating whether this structural profiling approach can be applied to other neurodegenerative diseases, such as Parkinson’s disease, and even cancer. Scripps Health is actively involved in numerous neurology research studies, including those focused on Alzheimer’s disease.