Developmental deletion of amyloid precursor protein precludes transcriptional and proteomic responses to brain injury

Introduction: Amyloid precursor protein (APP) undergoes striking changes following traumatic brain injury (TBI). Considering its role in the control of gene expression, we investigated whether APP regulates transcription and translation following TBI. Methods: We assessed brain morphology (n = 4-9 mice/group), transcriptome (n = 3 mice/group), proteome (n = 3 mice/group), and behavior (n = 17-27 mice/group) of wild-type (WT) and APP knock-out (KO) mice either untreated or 10-weeks following TBI. Results: After TBI, WT mice displayed transcriptional programs consistent with late stages of brain repair, hub genes were predicted to impact translation and brain proteome showed subtle changes. APP KO mice largely replicated this transcriptional repertoire, but showed no transcriptional nor translational response to TBI. Discussion: The similarities between WT mice following TBI and APP KO mice suggest that developmental APP deficiency induces a condition reminiscent of late stages of brain repair, hampering the control of gene expression in response to injury. Highlights: 10-weeks after TBI, brains exhibit transcriptional profiles consistent with late stage of brain repair. Developmental APP deficiency maintains brains perpetually in an immature state akin to late stages of brain repair. APP responds to TBI by changes in gene expression at a transcriptional and translational level. APP deficiency precludes molecular brain changes in response to TBI.

Citation

Lacovich, V., Čarna, M., Novotný, S. J., Wang, S., Texlová, K., Kovačovicova, K. L., Dragišić, N., Havas, D., Head, B. P., Geda, Y. E., Limbäck-Stokin, C., & Stokin, G. B. (2025). Developmental deletion of amyloid precursor protein precludes transcriptional and proteomic responses to brain injury. Alzheimer's & dementia : the journal of the Alzheimer's Association, 21(4), e70093. https://doi.org/10.1002/alz.70093

DOI

10.1002/alz.70093

URI

https://hdl.handle.net/20.500.14709/346

Usage rights

CC BY-NC-ND 4.0

License

https://creativecommons.org/licenses/by-nc-nd/4.0/