Advancements in Alzheimer’s Detection for Down Syndrome

Individuals with Down syndrome are at a significantly high risk of developing Alzheimer’s disease, yet they have often been overlooked in the development of blood tests for the condition. Recent progress indicates a potential shift in this trend. A study has found that two existing blood tests, effective in detecting Alzheimer’s in the general population, also show promising results for individuals with Down syndrome. The report published in Communications Medicine highlights an essential move towards easier and more accessible Alzheimer’s screening for this group, which traditionally relies on more invasive testing methods.

Blood Tests Offer New Hope

Research focused on two blood tests: Lumipulse G p-tau217/β-Amyloid 1-42 and PrecivityAD2. These tests identify amyloid buildup and abnormal tau proteins in the brain, indicators closely linked to Alzheimer’s disease that begin changing long before symptoms manifest. While blood tests have gained attention due to their simplicity compared to brain scans or spinal taps, individuals with Down syndrome have been underrepresented in studies assessing these tests’ effectiveness. Michael Rafii, clinical neurology professor at the Keck School of Medicine of USC and the study’s lead author, emphasized the transformative impact of these blood tests.

There is particular importance because people with Down syndrome are at exceptionally high risk for Alzheimer’s disease. The genetic alterations inherent in Down syndrome lead to increased amyloid accumulation, contributing to the condition’s high prevalence within this population.

Challenges in Diagnosing Alzheimer’s in Down Syndrome

Diagnosing Alzheimer’s in those with Down syndrome presents unique challenges. Dr. Yıldız Değirmenci, neurology professor at Medicana Health Group, stated that distinguishing new cognitive decline from intellectual disability requires careful consideration. Changes often appear in executive functioning, personality, or behavior rather than the memory loss commonly associated with Alzheimer’s in the general population.

The study enrolled 39 individuals with Down syndrome, who underwent both blood testing and PET scans. Researchers discovered that both blood tests accurately identified individuals with abnormal amyloid levels, developing preliminary thresholds for distinguishing Alzheimer’s-related brain pathology. This advancement suggests a future where simple blood draws may precede more complicated testing, an essential factor given the current diagnostic challenges like limited access to PET scans and invasive procedures such as lumbar puncture.

“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 ready to scale, reducing the burden on patients.”

Dr. Değirmenci emphasized the practical implications, noting that blood biomarkers should complement clinical history and cognitive assessments.

Future Directions for Blood Testing

Blood tests may offer additional benefits beyond Alzheimer’s detection. Conditions causing memory issues or behavioral changes have various causes. Reliable Alzheimer’s exclusion could facilitate the investigation into other issues like untreated depression or sleep apnea. Michael Rafii underscored this potential benefit for families seeking clarity on symptoms.

Researchers stressed the need for further study to broaden the application of these findings. Plans include validating tests in larger, diverse groups to establish the appropriate diagnostic thresholds. Rafii highlighted the challenges such as regulatory review, insurance coverage, and equitable access to specialists, emphasizing the importance of accompanying testing with proper counseling.

Despite hurdles, the study’s implications are already influencing future research. Blood-based screening will identify eligible participants for upcoming trials, including testing Alzheimer’s treatment donanemab in individuals with Down syndrome.

Inclusion remains a vital aspect of this research. Historically, people with Down syndrome have contributed significantly to Alzheimer’s biology understanding but have been absent from clinical trials. Rafii stressed the scientific and ethical imperative of inclusion, recognizing the valuable contribution of this population to Alzheimer’s research.

Study co-authors include Oliver Langford, Michael Donohue, Xiaoyu Zhou, Sonal Sukreet, Sara Abdel-Latif, and Robert Rissman from USC; Matthew Zammit from the University of Wisconsin–Madison; and Joel Braunstein from C2N Diagnostics. The study was supported by the National Institutes of Health.