Home News Plasma biomarkers can be used to detect tau pathology in Down syndrome

Plasma biomarkers can be used to detect tau pathology in Down syndrome

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Source/Disclosures


Disclosures:
Janelidze reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.


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Plasma p-tau217 proved an accurate blood-based biomarker of both tau and amyloid-beta pathological brain alterations for those with Down syndrome and may be used alone or with age as a covariate, per a study published in JAMA Neurology.

“[Down syndrome (DS)] is associated with a variety of clinical manifestations resulting from additional copies of protein-encoding genes located on chromosome 21, including the gene for the [amyloid precursor protein (APP)],” Shorena Janelidze, PhD, of the Clinical Memory Research Unit, department of clinical sciences at Lund University in Sweden, and colleagues wrote. “Overexpression of the APP gene in DS leads to accumulation of brain amyloid-beta and tau pathologies typical of Alzheimer’s disease.”


All white room where PET machine stands

Source: Adobe Stock.

Researchers aimed to determine which plasma biomarker combinations can accurately detect tau pathological brain changes in those with DS.

The cross-sectional, multicenter Alzheimer’s Biomarker Consortium-Down Syndrome study included 300 adults with DS, as well as a control group of 37 siblings without DS, enrolled between 2016 and 2019. Plasma p-tau217, glial fibrillary acidic protein (GFAP), amyloid beta42/40, neurofilament light (NfL) and total tau (t-tau); tau positron emission tomography (tau-PET); and amyloid beta-PET were the main exposures, whereas the primary outcome was tau-PET status. Secondary outcomes included amyloid beta-PET status and cognitive performance. Data were analyzed from August 2021 to April 2022.

Results showed that, among participants with DS who underwent plasma p-tau217 and GFAP analyses, 258 had other plasma biomarker data available and 119, 213, and 288 participants submitted to tau-PET, amyloid beta-PET and cognitive assessments, respectively.

Plasma p-tau217 and t-tau were significantly increased in amyloid beta-PET-positive tau-PET-positive (A+T+) DS and A+T– DS compared with A–T– DS, whereas GFAP was increased only in A+T+ DS. Plasma p-tau217 levels were also significantly higher in A+T+ DS than A+T– DS.

Researchers also found, in participants with DS, plasma p-tau217 and GFAP (but not other plasma biomarkers) were consistently associated with abnormal tau-PET and amyloid beta-PET status in models covaried for age (OR range, 1.59 [95% CI, 1.05-2.40] to 2.32 [95% CI, 1.36-3.96]). Data additionally revealed 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 most stinting model for amyloid beta-PET status included p-tau217, t-tau and age (AUC range, 0.93-0.95).

“The excellent performance of plasma p-tau217 in the present study indicated that it could be used even as a standalone blood-based biomarker,” Janelidze and colleagues wrote.

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