Decoding brain structure to stage Alzheimer's disease pathology in Down syndrome
Open accessAbstract
INTRODUCTION: Alzheimer's disease (AD) in Down syndrome (DS) is associated with changes in brain structure. It is unknown if thickness and volumetric changes can identify AD stages and if they are similar to other genetic forms of AD. METHODS: Magnetic resonance imaging scans were collected for 178 DS adults (106 nonclinical, 45 preclinical, and 27 symptomatic). Cortical thickness and subcortical volumes were compared between DS groups and evaluated as a staging metric using receiver operating characteristic analyses. Thickness patterns were compared to those previously reported in autosomal‐dominant AD (ADAD). RESULTS: Decreased parietal and temporal lobe thickness differentiated amyloid positivity (area under the curve [AUC] = 0.83) and impairment (AUC = 0.81), and slightly outperformed subcortical volumes (AUC = 0.8/0.74). Thickness differences in DS were more widespread, severe, and had better discriminative ability than ADAD. DISCUSSION: Cortical thickness can stage AD pathology in DS. Identification of brain regions affected by AD may aid in tracking disease course and evaluating treatment effects. Highlights: DSAD is associated with reduced temporal and parietal cortical thickness. DSAD is associated with smaller hippocampal and striatal volumes. Thickness differences can stage DSAD better than other forms of AD. DSAD thickness differences are more extensive and severe than ADAD.
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Recent natural history studies have highlighted evidence of accelerated AD progression in people who have DSAD, including a more rapid development of tau spread as measured by positron emission tomography and plasma phospho-tau217, and enhanced rates of cortical thinning, after normalising for amyloid-β accumulation.
“Recent natural history studies comparing the development of AD in the general population and DSAD have highlighted evidence of accelerated AD progression in people who have DSAD. This includes a more rapid development of tau spread as measured by positron emission tomography and plasma phospho-tau217 [60, 68, 72], and enhanced rates of cortical thinning [37], after normalising for amyloid-β accum”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [37]
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- Authors
- Kennedy, J. T., Wisch, J. K., Dincer, A., Roman, J., Gordon, B. A., Handen, B., Benzinger, T. L. S., Head, E., Mapstone, M., Christian, B. T., Tudorascu, D. L., Laymon, C. L., Hartley, S. L., Lao, P., Brickman, A. M., Zaman, S. H., Ances, B. M., & Consortia, T. A. A. D.
- Affiliations
- Washington University in St. Louis (US)
- University of Pittsburgh (US)
- University of California, Irvine (US)
- University of Wisconsin–Madison (US)
- Department of Radiology University of Pittsburgh Pittsburgh Pennsylvania USA
- Columbia University (US)
- University of Cambridge (GB)
- Corresponding author
- Ances, Beau M.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2025-01-14
- Volume
- 21
- Issue
- 2
- Pages
- e14519-e14519
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC11848172
- OpenAlex
- W4406372877
- Cited by
- 7
- References
- 34
- Citations by year
- 2026: 3 · 2025: 4
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Funders
- National Institute on Handicapped Research (NIHR203312)
- National Institute on Aging (U19AG068054, U19AG032438)
- Alzheimer's Association (SG‐20‐690363‐DIAN)
- Deutsches Zentrum für Neurodegenerative Erkrankungen
- Japan Agency for Medical Research and Development
- Korea Health Industry Development Institute
- Korea Display Research Corporation (HI21C0066)
- Instituto de Salud Carlos III
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Down syndrome, Alzheimer's disease
- MeSH terms
- Adult, Alzheimer Disease, Brain, Down Syndrome, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged
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