New blood tests accurately detect Alzheimer’s disease in adults with Down syndrome

A recent study suggests that newly developed blood tests can accurately detect signs of Alzheimer’s disease in adults with Down syndrome. These tests measure specific proteins in the blood, offering an easier and less invasive alternative to brain scans or spinal taps. The findings, published in the journal Communications Medicine, indicate that these accessible tests could soon help families and doctors identify Alzheimer’s changes earlier in this high-risk population.

People with Down syndrome are at an exceptionally high risk of developing Alzheimer’s disease. This is due to their genetics. Down syndrome is caused by an extra copy of chromosome 21. This specific chromosome contains the gene responsible for producing amyloid precursor protein.

Amyloid is a naturally occurring protein that can clump together to form plaques in the brain, a primary hallmark of Alzheimer’s disease. Because of this genetic duplication, nearly all individuals with Down syndrome develop these brain plaques by the age of 40.

These brain plaques damage surrounding cells and trigger another protein, called tau, to become tangled. When tau proteins tangle, they disrupt the brain’s internal transport system, leading to cell death and severe memory loss. The lifetime risk of developing Alzheimer’s exceeds 90 percent for people with Down syndrome, making it a leading cause of health complications as they age.

Recently, blood tests that measure specific forms of these proteins have become available for the general public. One such test measures a modified tau protein known as p-tau217. These blood-based diagnostics offer a massive improvement over traditional methods, which require either expensive radiation-based brain imaging or invasive spinal taps.

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Despite their benefits, these modern diagnostic tools have not been validated for individuals with Down syndrome. A team of scientists from the University of Southern California, the University of Wisconsin-Madison, and C2N Diagnostics evaluated whether these modern blood tests could accurately detect Alzheimer’s pathology in adults with Down syndrome. Their goal was to expand access to early detection methods for a group that is frequently left out of medical advancements.

The researchers analyzed data from 39 adults with Down syndrome. The participants ranged in age from 25 to 55, with an average age of 38.4 years. None of the participants had a formal diagnosis of dementia, though some had mild cognitive impairment.

Each participant underwent a brain scan known as positron emission tomography, commonly called a PET scan. A PET scan is a highly sensitive imaging technique that allows doctors to see amyloid plaques in the living brain. The researchers measured the amyloid levels using a standard scale called centiloids. Any score above 18 centiloids was categorized as having elevated brain amyloid.

Based on these brain scans, 20.5 percent of the participants, which was 8 out of 39 individuals, had elevated levels of amyloid. Within a 45-day window of their brain scans, the participants provided blood samples.

The research team tested the blood plasma using two different automated technologies. The first was an immunoassay called Lumipulse, which uses specific antibodies to measure the concentration of the p-tau217 protein. The second was a mass spectrometry test called PrecivityAD2, which weighs molecules to identify both p-tau217 and several other proteins, including different forms of amyloid.

The scientists found that both blood tests successfully identified which participants had elevated brain amyloid. The Lumipulse test accurately matched the PET scan results 90 percent of the time. The test achieved this accuracy by using a specific concentration threshold of 0.21 picograms per milliliter for the p-tau217 protein.

The mass spectrometry test performed similarly well, correctly identifying brain amyloid status with 92 percent accuracy. Both testing methods demonstrated high sensitivity and specificity. This means they were highly capable of identifying true positive cases of elevated amyloid and rarely returned false positive results. Statistical analyses showed an Area Under the Curve of 0.94 for Lumipulse and 0.91 for the mass spectrometry test, a metric indicating excellent diagnostic performance.

Interestingly, measuring amyloid proteins directly in the blood did not help the researchers predict brain amyloid levels in this group. In the general population, looking at the ratio of two specific amyloid proteins, known as amyloid-beta 42 and amyloid-beta 40, is often a reliable indicator of Alzheimer’s disease. These specific amyloid ratios showed no correlation with the PET scan results in this sample.

The researchers suspect this is due to the genetic nature of Down syndrome. Because individuals with Down syndrome produce abnormally high amounts of amyloid throughout their entire lives, the relative changes in blood amyloid concentrations might be too small to reliably detect early Alzheimer’s changes. The p-tau217 protein proved to be the most accurate blood-based marker.

The study provides encouraging evidence for the use of blood tests, but the sample size was small. Only eight participants in the study actually had elevated brain amyloid. The specific thresholds used to determine a positive or negative test result are preliminary. They will need to be tested and adjusted in much larger groups of people to ensure they work reliably.

The research only captured a single snapshot in time. The study did not track the participants over several years to see if those with positive blood tests eventually experienced cognitive decline or memory loss. Because the participants were mostly young and not yet showing severe symptoms, it is not completely certain how these blood markers relate to the actual onset of dementia.

The researchers were only able to compare the blood tests to amyloid PET scans. They lacked the data to compare the blood tests against brain scans that measure tau tangles, which is what the p-tau217 blood test is actually detecting.

Future research will involve applying these tests in larger clinical trials. Scientists plan to use these blood markers to identify eligible participants for new Alzheimer’s treatment studies. Expanding this research might lead to established guidelines that doctors can use to routinely screen adults with Down syndrome during regular checkups.

The study, “Exploring Automated Plasma Phospho-Tau217 Assays for the Diagnosis of Down Syndrome-Related Alzheimer’s Disease,” was authored by Zinayida Schlachetzki, Oliver Langford, Matthew Zammit, Michael C. Donohue, Xiaoyu Zhou, Sonal Sukreet, Sara Abdel-Latif, Joel B. Braunstein, Robert A. Rissman, and Michael S. Rafii.