Blood Biomarker Can Detect Tau Pathological Brain Changes in Down Syndrome

man with down syndrome on tablet
Researchers sought to identify which plasma biomarker combinations can accurately detect AD-related tau pathological brain changes in individuals with Down syndrome.

An accurate blood-based biomarker of both tau and amyloid-beta pathological brain changes in individuals with Down syndrome may be used alone or combined with an age covariate to help inform screening and enrichment plans for upcoming clinical trials of Alzheimer’s disease (AD). These are the findings of a study published in the Journal of the American Medical Association Neurology.

The overexpression of the amyloid precursor protein (APP) gene in Down syndrome results in tau pathologies and accumulation of brain amyloid-beta also common in AD. Prior studies have shown plasma biomarkers, in particular, phosphorylated tau, detects brain tau in AD.

Researchers sought to determine which plasma biomarkers can accurately detect tau brain changes in individuals with Down syndrome. The primary outcome was tau positron emission tomography (tau-PET) status, while secondary outcomes included amyloid-beta-PET status and cognitive performance. Other factors associated with outcomes of interest included plasma p-tau217, glial fibrillary acidic protein (GFAP), amyloid β42/40 (Aβ42/Aβ40), neurofilament light (NfL), and total tau (t-tau).

The researchers conducted a cross-sectional, multicenter Alzheimer’s Biomarker Consortium-Down Syndrome study that included 300 participants (mean age 45 years; 49.6% men) with Down syndrome who underwent analysis of plasma p-tau217 and GFAP, and 37 siblings without Down syndrome as a control group. The data were analyzed between August 2021 and April 2022.

Plasma p-tau217 and t-tau were significantly increased in amyloid-beta-PET-positive tau-PET-positive Down syndrome. In individuals with Down syndrome, plasma p-tau217 and GFAP biomarkers were consistently associated with abnormal tau-PET and amyloid-beta-PET status in models covaried for age (odds ratio range 1.59 [95% CI, 1.05-2.40] to 2.32 [95% CI, 1.36-3.96]; P <.03). Combining p-tau217 and age was best for detecting tau-PET abnormality. Only higher p-tau217 levels in multivariable models associated with worse performance on [Down Syndrome] Mental Status Examination and Cued Recall Test.

Moreover, a combination of p-tau217 and age performed best when detecting tau-PET abnormality in temporal and neocortical regions (area under the curve [AUC] range, 0.96-0.99), the researchers stated. They added that “the most parsimonious model” for amyloid-beta status included p-tau217 levels, t-tau, and age (AUC range, 0.93-0.95).

Study limitations included the lack of longitudinal data and underpowered sample size.

Researchers noted that, “The excellent performance of plasma p-tau217 in the present study indicates that it could be used even as a stand-alone blood-based biomarker enabling selection and inclusion of adults with [Down syndrome] in anti-AD clinical trials.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Janelidze S, Christian BT, Price J, et al. Detection of brain tau pathology in down syndrome using plasma biomarkers. JAMA Neurol. Published online July 5, 2022. doi:10.1001/jamaneurol.2022.1740