Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan - Summary - MDSpire

Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan

  • By

  • Jesse R. Pascual

  • Isabel Rivera

  • Halyma Nguyen

  • Phong T. Ngo

  • Alan Hoang

  • Elizabeth J. Andrews

  • Jeremy Rouanet

  • Sierra T. Wright

  • Lorena Sordo

  • Julia Kofler

  • Milos D. Ikonomovic

  • Florence Lai

  • Mark Mapstone

  • Bradley T. Christian

  • Benjamin L. Handen

  • Ira T. Lott

  • Eric Doran

  • Christy L. Hom

  • Jordan Harp

  • Frederick Schmitt

  • Dana L. Tudorascu

  • Beau M. Ances

  • Michael Phelan

  • Lei Liu

  • Lisi Flores-Aguilar

  • Elizabeth Head

  • March 22, 2026

  • 0 min

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Objective:

To quantify the neuropathology burdens of pThr181, pThr231, and pThr217 in the frontal cortex of individuals with Down syndrome (DS) and late-onset Alzheimer's disease (LOAD), specifically focusing on individuals aged 1 to 96 years, and to assess changes across the lifespan.

Key Findings:
  • Individuals with DS show a significantly more rapid accumulation of p-tau pathology compared to those with LOAD, indicating a critical difference in disease progression.
  • By age 40, virtually all individuals with DS exhibit Aβ and p-tau neuropathology, highlighting the urgent need for monitoring.
  • There is a differential age-associated increase in p-tau epitopes in DS across the lifespan, suggesting unique pathological trajectories.
Interpretation:

The study highlights the accelerated tau pathology in individuals with Down syndrome compared to typical late-onset Alzheimer's disease, suggesting a critical need for early intervention strategies tailored to this population.

Limitations:
  • The study is limited by the availability of postmortem tissue, which may not represent the broader population, and the exclusion of cases with mosaicism and partial trisomy, potentially affecting generalizability.
  • APOE genotype and Braak NFT staging data were not available for all groups, which may limit the understanding of genetic influences on pathology.
Conclusion:

The findings underscore the importance of monitoring tau pathology in individuals with Down syndrome as they age, given their heightened risk for Alzheimer's disease.

Original Source(s)

Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan

  • by Jesse R. Pascual, Isabel Rivera, Halyma Nguyen, Phong T. Ngo, Alan Hoang, Elizabeth J. Andrews, Jeremy Rouanet, Sierra T. Wright, Lorena Sordo, Julia Kofler, Milos D. Ikonomovic, Florence Lai, Mark Mapstone, Bradley T. Christian, Benjamin L. Handen, Ira T. Lott, Eric Doran, Christy L. Hom, Jordan Harp, Frederick Schmitt, Dana L. Tudorascu, Beau M. Ances, Michael Phelan, Lei Liu, Lisi Flores-Aguilar, Elizabeth Head

  • March 22, 2026

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