Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan.

Cross-sectionalActa neuropathologica· Mar 2026

Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan.

Jesse R Pascual, Isabel Rivera, Halyma Nguyen … Alzheimer’s Biomarkers Consortium–Down Syndrome (ABC-DS) Investigators

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NeuropathologyCross-sectionalQ1IF 8.5

Phosphorylated tau at threonine 231 rises sharply in Down syndrome brains at age 40

Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan.

Jesse R Pascual … Alzheimer’s Biomarkers Consortium–Down Syndrome (ABC-DS) Investigators

Acta neuropathologica · Mar 2026 · Q1 in Pathology

Methods

We analyzed postmortem brain samples of 98 individuals with late-onset alzheimer disease (late-onset AD), down syndrome with alzheimer disease neuropathology (DSAD), young down syndrome (below 40 years of age), and age-matched neurotypical controls, ranging from 1 to 96 years of age.

n = 98 individuals

age 40

Results

age 40

marks when p-tau231 starts climbing sharply in Down syndrome

n = 98 individuals

More results

Fluid alzheimer disease biomarker studies highlight an increase in several phosphorylated tau (p-tau) epitopes in down syndrome.

Immunohistochemical and digital pathology measures of p-tau epitopes at threonine 181 (pThr181), threonine 217 (pThr217), and threonine 231 (pThr231) burdens in the frontal cortex were compared across groups.

More results

We observed similar Thr181, Thr217, and Thr231 burdens between DSAD and late-onset AD, despite DSAD cases being younger on average.

Observed Thr181, Thr217, and Thr231 burdens were higher in DSAD compared to young down syndrome and neurotypical controls.

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Conclusion

Our results have the potential to inform future associations between neuropathological and biofluid and neuroimaging biomarker measures of p-tau epitopes.

Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan.

Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan.

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