Dataset Information

Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.

ABSTRACT: Cerebral visual impairments (CVIs) is an umbrella term that categorizes miscellaneous visual defects with parallel genetic brain disorders. While the manifestations of CVIs are diverse and ambiguous, molecular diagnostics stand out as a powerful approach for understanding pathomechanisms in CVIs. Nevertheless, the characterization of CVI disease cohorts has been fragmented and lacks integration. By revisiting the genome-wide and phenome-wide association studies (GWAS and PheWAS), we clustered a handful of renowned CVIs into five ontology groups, namely ciliopathies (Joubert syndrome, Bardet-Biedl syndrome, Alstrom syndrome), demyelination diseases (multiple sclerosis, Alexander disease, Pelizaeus-Merzbacher disease), transcriptional deregulation diseases (Mowat-Wilson disease, Pitt-Hopkins disease, Rett syndrome, Cockayne syndrome, X-linked alpha-thalassaemia mental retardation), compromised peroxisome disorders (Zellweger spectrum disorder, Refsum disease), and channelopathies (neuromyelitis optica spectrum disorder), and reviewed several mutation hotspots currently found to be associated with the CVIs. Moreover, we discussed the common manifestations in the brain and the eye, and collated animal study findings to discuss plausible gene editing strategies for future CVI correction.

SUBMITTER: Chang KJ

PROVIDER: S-EPMC9456058 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.

Chang Kao-Jung KJ Wu Hsin-Yu HY Yarmishyn Aliaksandr A AA Li Cheng-Yi CY Hsiao Yu-Jer YJ Chi Yi-Chun YC Lo Tzu-Chen TC Dai He-Jhen HJ Yang Yi-Chiang YC Liu Ding-Hao DH Hwang De-Kuang DK Chen Shih-Jen SJ Hsu Chih-Chien CC Kao Chung-Lan CL

International journal of molecular sciences 20220826 17

Cerebral visual impairments (CVIs) is an umbrella term that categorizes miscellaneous visual defects with parallel genetic brain disorders. While the manifestations of CVIs are diverse and ambiguous, molecular diagnostics stand out as a powerful approach for understanding pathomechanisms in CVIs. Nevertheless, the characterization of CVI disease cohorts has been fragmented and lacks integration. By revisiting the genome-wide and phenome-wide association studies (GWAS and PheWAS), we clustered a ...[more]

PMID: 36077104

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Project description:Large-scale clinical research studies often incorporate neuroimaging biomarkers to understand underlying pathologic changes that occur in aging and neurodegenerative disease and are associated with cognitive decline and clinical impairment. Of particular interest are neuroimaging methods designed to understand various aspects of cerebrovascular disease that can lead to dementia and also co-occur with neurodegenerative diseases such as Alzheimer's disease. Neurovascular 4D flow magnetic resonance imaging is one such method that measures hemodynamic characteristics of medium-large cerebral vessels, but it remains unclear how measures derived from 4D flow imaging including pulsatility index, cerebral blood flow, and cross-sectional area relate to underlying pathologic changes in cerebral arteries and downstream cerebrovascular pathology. For example, pulsatility index is thought to be a marker of vessel compliance, which may be due to fibrotic and/or atherosclerotic changes. This observational study investigates imaging-pathologic correlates of cerebral artery 4D flow MRI in 20 initial brain donors (mean (SD) age at death 78.2 (10.3) years; 3.2 (1.4) years from MRI to autopsy) from the Wisconsin Alzheimer's Disease Research Center that underwent antemortem imaging and postmortem assessment of cerebral artery and brain pathology to identify possible pathologic correlates of 4D flow MRI. Our results suggest that 4D flow MRI measures recapitulate expected hemodynamic and structural relationships across cerebral arteries, but also that measures like MRI cross-sectional area may reflect arterial fibrosis whereas mean blood flow may indicate downstream cerebrovascular disease including white matter rarefaction and arteriolosclerosis. In contrast, associations were minimal with pulsatility index and cerebral artery or brain pathology across participants but were moderate across arterial segments. To our knowledge, this is the first study to investigate pathologic correlates of antemortem 4D flow MRI in cerebral arteries. These results provide preliminary insights regarding the pathologic processes contributing to cerebral artery hemodynamics measured with 4D flow MRI that will help inform interpretation of large-scale clinical aging and dementia studies utilizing this method. Future work with larger samples is needed to confirm these findings.

Dataset Information

Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.

Publications

Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.

Similar Datasets

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