Document Type
Article
Publication Date
8-1-2023
Keywords
Brain regions, Intelligence, Memory, Dp71, Dp140, Alzheimer’s disease
Abstract
Introduction: Documented Duchenne Muscular Dystrophy (DMD) biomarkers are confined to Caucasians and are poor indicators of cognitive difficulties and neuropsychological alterations.
Materials and methods: This study correlates serum protein signatures with cognitive performance in DMD patients of South Asian origin. Study included 25 DMD patients aged 6–16 years. Cognitive profiles were assessed by Wechsler Intelligence Scale for Children. Serum proteome profiling of 1317 proteins was performed in eight DMD patients and eight age-matched healthy volunteers.
Results: Among the several novel observations we report, better cognitive performance in DMD was associated with increased serum levels of MMP9 and FN1 but decreased Siglec-3, C4b, and C3b. Worse cognitive performance was associated with increased serum levels of LDH-H1 and PDGF-BB but reduced GDF-11, MMP12, TPSB2, and G1B. Secondly, better cognitive performance in Processing Speed (PSI) and Perceptual Reasoning (PRI) domains was associated with intact Dp116, Dp140, and Dp71 dystrophin isoforms while better performance in Verbal Comprehension (VCI) and Working Memory (WMI) domains was associated with intact Dp116 and Dp140 isoforms. Finally, functional pathways shared with Alzheimer’s Disease (AD) point towards an astrocyte-centric model for DMD.
Conclusion: Astrocytic dysfunction leading to synaptic dysfunction reported previously in AD may be a common pathogenic mechanism underlying both AD and DMD, linking protein alterations to cognitive impairment. This new insight may pave the path towards novel therapeutic approaches targeting reactive astrocytes.
Publisher Attribution
2405-8440/© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Recommended Citation
Wijekoon, Nalaka; Gonawala, Lakmal; Ratnayake, Pyara; Dissanayaka, Pulasthi; Gunarathne, Isuru; Amaratunga, Dhammika; Liyanage, Roshan; Senanayaka, Sunethra; Wijesekara, Saraji; Gunasekara, Hemal H.; Vanarsa, Kamala; Castillo, Jessica; Hathout, Yetrib; Dalal, Ashwin; Steinbusch, Harry W.M.; Hoffman, Eric; Mohan, Chandra; and de Silva, K. Ranil D., "Integrated genomic, proteomic and cognitive assessment inDuchenne Muscular Dystrophy suggest astrocyte centric pathology" (2023). Pharmacy Faculty Scholarship. 77.
https://orb.binghamton.edu/pharmacy_fac/77
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Comments
https://doi.org/10.1016/j.heliyon.2023.e18530