Early Detection of White Matter Integrity Changes in Down Syndrome: The Promise of PSMD as a Sensitive Biomarker

Topic: Brain proteins, microglia and lab models

PSMD was more strongly associated with age in DS (rho=0.56; p <0.001) than in HC (rho=0.38, p <0.001; Figure 1A), with regression lines starting to diverge at age 42. No significant effects were found for sex, APOEε4 status, intellectual disability, or VRF (Figure 1C-D-E). PSMD increased linearly along the AD continuum (HC<aDS<pDS=dDS; Figure 1B), and correlated with CSF biomarkers of AD and neurodegeneration (Figure 2A-B-C). PSMD increased significantly in DS individuals with at least one microbleed (p = 0.003, Figure 2D) and strongly correlated with WMH (rho=0.56, p <0.001; Figure 2E). In DS, PSMD changed approximately 10-15 years before the onset of AD symptoms and linearly increased with AD clinical stages, AD pathology, and SVD metrics. These findings underscore the potential of PSMD as a sensitive biomarker for detecting early WM alterations in adults with DS.

Key findings

• PSMD was more strongly associated with age in DS (rho=0.56; p <0.001) than in HC (rho=0.38, p <0.001; Figure 1A), with regression lines starting to diverge at age 42.
• No significant effects were found for sex, APOEε4 status, intellectual disability, or VRF (Figure 1C-D-E).
• PSMD increased linearly along the AD continuum (HC<aDS<pDS=dDS; Figure 1B), and correlated with CSF biomarkers of AD and neurodegeneration (Figure 2A-B-C).
• PSMD increased significantly in DS individuals with at least one microbleed (p = 0.003, Figure 2D) and strongly correlated with WMH (rho=0.56, p <0.001; Figure 2E).
• In DS, PSMD changed approximately 10-15 years before the onset of AD symptoms and linearly increased with AD clinical stages, AD pathology, and SVD metrics.

Why it matters

This cross-sectional study found that a diffusion imaging marker of white matter damage increased along the Alzheimer's continuum in people with Down syndrome and changed about 10-15 years before symptoms. It suggests the marker may help detect early white matter changes, but it does not test any treatment, cure or prevention.

Study details

• Study designcross-sectional
• Participants70
• Effect size47.14%
• Evidence strengthLow

Read the original

• DOI: 10.1002/alz70862_109982
• PubMed: 41433511
• Original source →
• Free full text: Alzheimer s & Dementia →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{morcillonieto2025-41433511,
  author  = {Morcillo-Nieto, Alejandra Omaira and Arriola‐Infante, José Enrique and Franquesa‐Mullerat, María and Zsadanyi, Sára E. and Vaqué‐Alcázar, Lídia and Aranha, Mateus Rozalem and Parra, Jose Allende and Zhao, Zili and others},
  title   = {{Early Detection of White Matter Integrity Changes in Down Syndrome: The Promise of PSMD as a Sensitive Biomarker}},
  journal = {Alzheimer s \& Dementia},
  year    = {2025},
  doi     = {10.1002/alz70862_109982},
  pmid    = {41433511},
  url     = {https://doi.org/10.1002/alz70862_109982}
}

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