RT Journal Article
SR Electronic
T1 Imaging Transcriptomics of Brain Functional Alterations in MS and Neuromyelitis Optica Spectrum Disorder
JF American Journal of Neuroradiology
JO Am. J. Neuroradiol.
FD American Society of Neuroradiology
SP 1901
OP 1909
DO 10.3174/ajnr.A8480
VO 45
IS 12
A1 Li, Yuna
A1 Sun, Jun
A1 Zhuo, Zhizheng
A1 Guo, Min
A1 Duan, Yunyun
A1 Xu, Xiaolu
A1 Tian, Decai
A1 Li, Kuncheng
A1 Zhou, Fuqing
A1 Li, Haiqing
A1 Zhang, Ningnannan
A1 Han, Xuemei
A1 Shi, Fudong
A1 Li, Yongmei
A1 Zhang, Xinghu
A1 Liu, Yaou
YR 2024
UL http://www.ajnr.org/content/45/12/1901.abstract
AB BACKGROUND AND PURPOSE: The underlying transcriptomic signatures driving brain functional alterations in MS and neuromyelitis optica spectrum disorder (NMOSD) are still unclear.MATERIALS AND METHODS: Regional fractional amplitude of low-frequency fluctuation (fALFF) values were obtained and compared among 209 patients with MS, 90 patients with antiaquaporin-4 antibody (AQP4)+ NMOSD, 49 with AQP4− NMOSD, and 228 healthy controls from a discovery cohort. We used partial least squares (PLS) regression to identify the gene transcriptomic signatures associated with disease-related fALFF alterations. The biologic process and cell type–specific signature of the identified PLS genes were explored by enrichment analysis. The correlation between PLS genes and clinical variables was explored. A prospective independent cohort was used to validate the brain fALFF alterations and the repeatability of identified genes.RESULTS: MS, AQP4+ NMOSD, and AQP4− NMOSD showed decreased fALFF in cognition-related regions and deep gray matter, while NMOSD (both AQP4+ and AQP4−) additionally demonstrated lower fALFF in the visual region. The overlapping PLS1− genes (indicating that the genes were overexpressed as regional fALFF decreased) were enriched in response to regulation of the immune response in all diseases, and the PLS1− genes were specifically enriched in the epigenetics profile in MS, membrane disruption and cell adhesion in AQP4+ NMOSD, and leukocyte activation in AQP4− NMOSD. For the cell type transcriptional signature, microglia and astrocytes accounted for the decreased fALFF. The fALFF-associated PLS1− genes directly correlated with Expanded Disability Status Scale of MS and disease duration across disorders.CONCLUSIONS: We revealed the functional activity alterations and their underlying shared and specific gene transcriptional signatures in MS, AQP4+ NMOSD, and AQP4− NMOSD.AHBAAllen Human Brain AtlasAQP4antiaquaporin-4 antibodyEDSSExpanded Disability Status ScalefALFFfractional amplitude of low-frequency fluctuationFDRfalse discovery rateGOgene ontologyHChealthy controlsKEGGKyoto Encyclopedia of Genes and GenomesNMOSDneuromyelitis optica spectrum disorderPASTAParamedic Acute Stroke Treatment AssessmentpFDRP value with false discovery rate correctedPLSpartial least squaresrsfMRIresting-state fMRI