Blood tests show promise for Alzheimer's detection in Down syndrome patients

A person with Down syndrome walks into a clinic complaining of memory problems or behavioral changes. The doctor has limited tools to figure out what's happening. A brain scan requires a trip to a specialized center and a dose of radiation. A spinal tap means a needle in the spine. Neither is routine. Neither is easy. Now there's another option: a blood test, drawn like any other, that can tell whether Alzheimer's disease is the culprit.

For decades, this population has been invisible in the race to improve Alzheimer's diagnosis. People with Down syndrome face a staggering reality: by age 40, nearly all of them have amyloid plaques accumulating in their brains—the hallmark of Alzheimer's pathology. Over their lifetime, more than 90 percent will develop the disease. Alzheimer's is now the leading cause of death in people with Down syndrome over 35. Yet when the FDA approved Lumipulse G p-tau217, a blood test that detects early Alzheimer's changes, in 2025, people with Down syndrome were left out. The test had never been studied in them.

Researchers at USC's Epstein Family Alzheimer's Therapeutic Research Institute decided to change that. In a study published in Communications Medicine, they enrolled 39 people with Down syndrome and tested two blood tests—Lumipulse G p-tau217 and PrecivityAD2—against the gold standard: positron-emission tomography, or PET imaging of the brain. Both blood tests accurately detected abnormal amyloid buildup. Using statistical methods, the team established preliminary diagnostic thresholds tailored to people with Down syndrome that performed nearly as well as thresholds used in the general population.

The implications are immediate and practical. Blood tests are cheaper, faster, and far less burdensome than the alternatives. A person doesn't need to travel to a specialized medical center or endure radiation exposure. There's no lumbar puncture, no needle in the spine. "The blood test is much more accessible as a screening test," said Zinayida Schlachetzki, the study's first author. "It is easier to perform, less expensive and readily scalable, and it places substantially less burden on patients." For families trying to understand why a loved one is struggling, the ability to rule out Alzheimer's opens a door to other explanations—untreated depression, sleep apnea, or other treatable conditions.

The biology linking Down syndrome and Alzheimer's is now well understood. Down syndrome results from an extra copy of chromosome 21. That same duplication drives higher levels of amyloid production, the protein that clumps and damages brain cells. In Alzheimer's disease generally, amyloid triggers chemical changes in tau proteins, which normally act as scaffolding and transport systems inside neurons. When tau is damaged, it tangles and accumulates, killing nerve cells. People with Down syndrome are essentially living in a state of accelerated amyloid accumulation from birth, making them a unique window into Alzheimer's biology. "This population taught us so much about the biology of Alzheimer's," said Michael Rafii, the study's corresponding author and medical director of the institute. "It's sad, and wrong, to see them excluded from clinical trials."

The research comes at a pivotal moment. Next month, the team will launch a clinical trial testing donanemab, an FDA-approved Alzheimer's drug, in people with Down syndrome. Blood tests will be used to identify who has elevated brain amyloid and is eligible to participate. This is the first time people with Down syndrome will have systematic access to a leading-edge Alzheimer's treatment, and it hinges on the ability to diagnose them accurately and non-invasively. The researchers plan to validate their findings in a larger cohort, but the current results are already reshaping what's possible.

For a population that has long been an afterthought in precision medicine, the shift is significant. Rafii's message to families is direct: "If you have a family member with Down syndrome, know that there's hope on the horizon for an accurate blood test to help discern whether any symptoms they show are because of Alzheimer's disease or something else." The blood test won't cure Alzheimer's. But it offers something that has been missing for too long: the chance to know what's happening, and the chance to act early, when treatment might matter most.