Study Compares Tau Spread in People With Down Syndrome, Alzheimer Disease

In a recent cross-sectional, observational study comparing the tau spread in people with Down syndrome and autosomal-dominant Alzheimer disease, researchers found differences in distribution, timing, and magnitude between the two cohorts.

“These differences might have important implications; differences in the temporal pattern of tau accumulation might influence the timing of drug administration in clinical trials, whereas differences in the spatial pattern and magnitude of tau burden might affect disease progression,” Wisch and colleagues wrote in their study.

Patients with Down syndrome and autosomal-dominant Alzheimer disease both contend with pathological brain changes at a young age, most notably, the accumulation of amyloid and tau.

“Studies including these cohorts could, therefore, improve our understanding of the early pathogenesis of Alzheimer disease and be useful when designing preventive interventions targeted at disease pathology or when planning clinical trials,” the researchers explained in their study.

>> Video: Age at Menopause, Delayed Hormone Therapy Linked to Elevated Levels of Tau Protein

For their study, Wisch and colleagues collected patient data from two cohort studies: the Dominantly Inherited Alzheimer's Network studies (DIAN-OBS and DIAN-TU) and the Alzheimer Biomarkers Consortium–Down Syndrome study. The DIAN-OBS and DIAN-TU studies included participants with autosomal-dominant Alzheimer disease genetic mutations and non-carrier familial controls from Australia, Europe, and the United States between 2008 and 2022. The Alzheimer Biomarkers Consortium–Down Syndrome study included those with Down syndrome and sibling controls from the United Kingdom and United States who were recruited between 2015 and 2021. Researchers performed magnetic resonance imaging and tau positron emission tomography (PET) imaging on all participants.

A total of 137 adults with Down syndrome (mean age, 38.5 years; 54% male), 49 adults with autosomal-dominant Alzheimer disease (mean age, 43.9 years; 55% female), and 85 familial controls (mean age, 41.5 years; 67% female) were included in the study. Most of the participants also completed amyloid PET scan within 3 years of tau PET imaging.

The results indicated that the progression of amyloid to tau is similar for people Down syndrome and those with autosomal-dominant Alzheimer disease. The accumulation of both amyloid and tau were found in similar areas of the brain—the medial temporal regions—in both cohorts, though the Down syndrome cohort also observed tau PET burden in the subcortical region as well.

However, people with Down syndrome had greater concentrations of tau compared with those with autosomal-dominant Alzheimer disease, and those in the Down syndrome cohort also had increases in tau that were more strongly associated with increases in amyloid compared with the Alzheimer disease cohort.

“Although the general progression of amyloid followed by tau is similar for people Down syndrome and people with autosomal-dominant Alzheimer disease, we found subtle differences in the spatial distribution, timing, and magnitude of the tau burden between these two cohorts,” the researchers concluded.

Reference:
Wisch JK, McKay NS, Boerwinkle AH, et al. Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study. Lancet Neurol. 2024;23(5):500-510. doi:10.1016/S1474-4422(24)00084-X