Brain damage and gene expression across hereditary spastic paraplegia subtypes
KR Servelhere, TJR Rezende, FD de Lima… - Movement …, 2021 - Wiley Online Library
KR Servelhere, TJR Rezende, FD de Lima, MR de Brito, RF de Franca Nunes, RF Casseb…
Movement Disorders, 2021•Wiley Online LibraryBackground Spinal cord has been considered the main target of damage in hereditary
spastic paraplegias (HSPs), but mounting evidence indicates that the brain is also affected.
Despite this, little is known about the brain signature of HSPs, in particular regarding
stratification for specific genetic subtypes. Objective We aimed to characterize cerebral and
cerebellar damage in five HSP subtypes (9 SPG3A, 27 SPG4, 10 SPG7, 9 SPG8, and 29
SPG11) and to uncover the clinical and gene expression correlates. Methods We obtained …
spastic paraplegias (HSPs), but mounting evidence indicates that the brain is also affected.
Despite this, little is known about the brain signature of HSPs, in particular regarding
stratification for specific genetic subtypes. Objective We aimed to characterize cerebral and
cerebellar damage in five HSP subtypes (9 SPG3A, 27 SPG4, 10 SPG7, 9 SPG8, and 29
SPG11) and to uncover the clinical and gene expression correlates. Methods We obtained …
Background
Spinal cord has been considered the main target of damage in hereditary spastic paraplegias (HSPs), but mounting evidence indicates that the brain is also affected. Despite this, little is known about the brain signature of HSPs, in particular regarding stratification for specific genetic subtypes.
Objective
We aimed to characterize cerebral and cerebellar damage in five HSP subtypes (9 SPG3A, 27 SPG4, 10 SPG7, 9 SPG8, and 29 SPG11) and to uncover the clinical and gene expression correlates.
Methods
We obtained high‐resolution brain T1 and diffusion tensor image (DTI) datasets in this cross‐sectional case–control study (n = 84). The MRICloud, FreeSurfer, and CERES‐SUIT pipelines were employed to assess cerebral gray (GM) and white matter (WM) as well as the cerebellum.
Results
Brain abnormalities were found in all but one HSP group (SPG3A), but the patterns were gene‐specific: basal ganglia, thalamic, and posterior WM involvement in SPG4; diffuse WM and cerebellar involvement in SPG7; cortical thinning at the motor cortices and pallidal atrophy in SPG8; and widespread GM, WM, and deep cerebellar nuclei damage in SPG11. Abnormal regions in SPG4 and SPG8 matched those with higher SPAST and WASHC5 expression, whereas in SPG7 and SPG11 this concordance was only noticed in the cerebellum.
Conclusions
Brain damage is a conspicuous feature of HSPs (even for pure subtypes), but the pattern of abnormalities is genotype‐specific. Correlation between brain structural damage and gene expression maps is different for autosomal dominant and recessive HSPs, pointing to distinct pathophysiological mechanisms underlying brain damage in these subgroups of the disease. © 2021 International Parkinson and Movement Disorder Society
Wiley Online Library以上显示的是最相近的搜索结果。 查看全部搜索结果