| Autor: |
Edwards, Natalie C., Lao, Patrick J., Sedaghat, Amirreza, Rizvi, Batool, O'Bryant, Sid E., Mapstone, Mark, Tudorascu, Dana, Handen, Benjamin L., Christian, Bradley T., Wilcock, Donna M., Gutierrez, Jose, Head, Elizabeth, Brickman, Adam M. |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2023 Supplement 13, Vol. 19, p1-2, 2p |
| Abstrakt: |
Background: By age 40 over 90% of adults with Down syndrome (DS) develop Alzheimer's disease (AD) pathology and most progress to dementia. Despite having fewer systemic vascular risk factors than neurotypical adults, recent studies demonstrate evidence of significant cerebrovascular disease in individuals with DS that track with the clinical progression of AD, suggesting a role for cerebrovascular disease that is not attributable solely to exposure to vascular risk factors. In the current study, we examined the codependency between white matter hyperintensity (WMH) volume, a marker of small vessel cerebrovascular disease, and AD pathophysiology, indexed with plasma AD biomarkers, in adults with DS. Method: One hundred eighty‐seven participants from the Alzheimer Biomarkers Consortium – Down Syndrome (mean[SD] = 45.1[9.4] years) with available MRI and plasma biomarker data were included in the study. Whole‐brain WMH volumes were derived from T2‐weighted FLAIR MRI scans with in‐house software and plasma p‐tau217, Aβ42/Aβ40, and neurofilament light (NfL) concentrations were measured with SIMOA assays. Separate general linear models tested the association of WMH volume with each of the three biomarker concentrations; subsequent models were stratified by age, based on the median (46 years old). Result: Higher WMH volume was associated with increased p‐tau217 and NfL concentrations but not with Aβ. In stratified analyses, the association between WMH and NfL concentration was stronger in younger adults than in older adults whereas the association between WMH and p‐tau217 concentration was stronger in older adults than in younger adults. Conclusion: Our findings suggest a co‐dependency of cerebrovascular disease with tau pathology and neurodegeneration in adults with Down syndrome. Cerebrovascular disease may promote neurodegenerative changes in early adulthood and tau changes in later adulthood. The additional or alternative possibility that tau and neurodegeneration promote white matter changes cannot be ruled out in these cross sectional analyses. Future work will address the relative temporal emergence of these markers in adults with DS. [ABSTRACT FROM AUTHOR] |
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