| Autor: |
van der Ende, Emma L., in 't Veld, Sjors G.J.G., Hanskamp, Iris, Van der lee, Sven J, Dijkstra, Janna I.R., van Swieten, John C., Irwin, David J., Chen‐Plotkin, Alice, Hu, William T., Lemstra, Afina W., Pijnenburg, Yolande A.L., van der Flier, Wiesje M., del Campo, Marta, Teunissen, Charlotte E., Vermunt, Lisa |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2023 Supplement 14, Vol. 19, p1-2, 2p |
| Abstrakt: |
Background: Autosomal dominant Alzheimer's disease (ADAD) offers a unique opportunity to study pathophysiological changes in a relatively young population with few comorbidities. A comprehensive investigation of proteome changes occurring in ADAD could provide valuable insights into AD‐related biological mechanisms and uncover novel biomarkers and therapeutic targets. Furthermore, ADAD might serve as a model for sporadic AD, but in‐depth proteome comparisons are lacking. We aimed to identify dysregulated CSF proteins in ADAD and determine the degree of overlap with sporadic AD. Method: Using proximity extension‐based immunoassays (PEA) by Olink, we measured 1472 proteins in CSF of APP or PSEN1 mutation carriers (n = 22) and age‐ and sex‐matched controls (n = 20) from the Amsterdam Dementia Cohort. We compared protein abundance between groups using two‐sided t‐tests and identified enriched biological pathways. Using the same protein panels in paired plasma samples, we investigated correlations between CSF proteins and their plasma counterparts. Finally, we compared our results with recently published PEA data from an international cohort of sporadic AD (n = 230) and non‐AD dementias (n = 301). All analyses were false discovery rate‐corrected. Result: We detected 66 differentially abundant CSF proteins (65 increased, one decreased) in ADAD compared to controls (q<0.05). The most strongly upregulated proteins (fold change >1.8) were related to immunity (CHIT1, ITGB2, SMOC2), cytoskeletal structure (MAPT, NEFL) and tissue remodeling (TMSB10, MMP‐10). Significant CSF‐plasma correlations were found for the upregulated proteins SMOC2 and LILR1B. 36 of the 66 differentially expressed proteins had been previously measured in the sporadic dementias cohort, 34 of which (94%) were also significantly upregulated in sporadic AD, with a strong correlation between the fold changes of these proteins in both cohorts (rs = 0.730, p<0.001). 29 of these 36 proteins (81%) were also upregulated among non‐AD patients with suspected AD co‐pathology. Conclusion: This CSF proteomics study demonstrates substantial biochemical similarities between ADAD and sporadic AD, suggesting involvement of the same biological processes. Besides known AD‐related proteins, we identified several relatively novel proteins, such as TMSB10, MMP‐10 and SMOC2, which have potential as novel biomarkers. With shared pathophysiological CSF changes, ADAD study findings might be translatable to sporadic AD, which could greatly expedite therapy development. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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