Frequency of mixed neuropathologies in individuals with down syndrome with and without Alzheimer's dementia - Summary - MDSpire

Frequency of mixed neuropathologies in individuals with down syndrome with and without Alzheimer's dementia

  • By

  • Lisi Flores-Aguilar

  • Thomas D. Zaikos

  • Isabel Rivera

  • Sierra T. Wright

  • Jerry Lou

  • Brianna Gawronski

  • Lourdes Gonzalez

  • Jillian V. Berry

  • Jeremy Rouanet

  • Natalie C. Edwards

  • Dan K. Hoang

  • Kevin Wood

  • Ann-Charlotte Granholm

  • Elliott J. Mufson

  • Edwin S. Monuki

  • Milos D. Ikonomovic

  • Julia Kofler

  • Eric W. Doran

  • Ira T. Lott

  • Minodora O. Totoiu

  • Christy L. Hom

  • Florence Lai

  • William H. Yong

  • Frederick A. Schmitt

  • Jordan Harp

  • Peter T. Nelson

  • Jose Gutierrez

  • Patrick J. Lao

  • Donna M. Wilcock

  • Adam M. Brickman

  • Elizabeth Head

  • May 15, 2026

  • 0 min

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Objective:

To characterize the frequency and spectrum of Alzheimer's disease neuropathologic change (ADNC) and common co-pathologies in adults with Down syndrome (DS), and to describe the neuropathological profile of cognitively stable individuals with DS, emphasizing the distinction between ADNC and co-pathologies.

Key Findings:
  • ADNC is nearly universal in adults with DS, but the onset of dementia varies, indicating potential resilience factors.
  • Co-pathologies such as CAA, LP, LATE-NC, and HS are present in adults with DS, suggesting a multifactorial basis for dementia.
  • Individuals with DS without dementia may exhibit a distinct neuropathological profile compared to those with dementia, warranting further investigation.
Interpretation:

The presence of co-pathologies in DS suggests that dementia may arise from multiple interacting pathologies rather than a single process, highlighting the complexity of AD in this population and the need for targeted interventions.

Limitations:
  • Small sample sizes in previous studies limit generalizability, particularly in understanding the full spectrum of co-pathologies.
  • Exploratory comparisons between dementia groups due to the small number of individuals without dementia may lead to inconclusive results.
Conclusion:

Understanding the neuropathological profiles of individuals with DS, particularly those who remain cognitively stable, may provide insights into resilience and resistance mechanisms against Alzheimer's disease, with potential implications for clinical practice.

Original Source(s)

Frequency of mixed neuropathologies in individuals with down syndrome with and without Alzheimer's dementia

  • by Lisi Flores-Aguilar, Thomas D. Zaikos, Isabel Rivera, Sierra T. Wright, Jerry Lou, Brianna Gawronski, Lourdes Gonzalez, Jillian V. Berry, Jeremy Rouanet, Natalie C. Edwards, Dan K. Hoang, Kevin Wood, Ann-Charlotte Granholm, Elliott J. Mufson, Edwin S. Monuki, Milos D. Ikonomovic, Julia Kofler, Eric W. Doran, Ira T. Lott, Minodora O. Totoiu, Christy L. Hom, Florence Lai, William H. Yong, Frederick A. Schmitt, Jordan Harp, Peter T. Nelson, Jose Gutierrez, Patrick J. Lao, Donna M. Wilcock, Adam M. Brickman, Elizabeth Head

  • May 15, 2026

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