An Integrated Approach to Maintenance Human Factors

Allen, Jerry; Rankin, William L.

doi:10.4271/972594

Cited by 1 publication

(1 citation statement)

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“…Gene expression was assayed with custom designed arrays, and samples were mapped to anatomical locations accompanied with Montreal Neurological Institute (MNI) space coordinates. Details of the methods and quality controls are specified in the Microarray Survey Technical White Paper 23 …”

Section: Methodsmentioning

confidence: 99%

Longitudinal Effects of Asymptomatic C9orf72 Carriership on Brain Morphology

Veenhuijzen

Westeneng

Tan

et al. 2022

Annals of Neurology

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Objective: We investigated effects of C9orf72 repeat expansion and gene expression on longitudinal cerebral changes before symptom onset. Methods: We enrolled 79 asymptomatic family members (AFMs) from 9 families with C9orf72 repeat expansion. Twenty-eight AFMs carried the mutation (C9+). Participants had up to 3 magnetic resonance imaging (MRI) scans, after which we compared motor cortex and motor tracts between C9+ and C9À AFMs using mixed effects models, incorporating kinship to correct for familial relations and lessen effects of other genetic factors. We also compared cortical, subcortical, cerebellar, and connectome structural measurements in a hypothesis-free analysis. We correlated regional C9orf72 expression in donor brains with the pattern of cortical thinning in C9+ AFMs using meta-regression. For comparison, we included 42 C9+ and 439 C9À patients with amyotrophic lateral sclerosis (ALS) in this analysis. Results: C9+ AFM motor cortex had less gyrification and was thinner than in C9À AFMs, without differences in motor tracts. Whole brain analysis revealed thinner cortex and less gyrification in parietal, occipital, and temporal regions, smaller thalami and right hippocampus, and affected frontotemporal connections. Thinning of bilateral precentral, precuneus, and left superior parietal cortex was faster in C9+ than in C9À AFMs. Higher C9orf72 expression correlated with thinner cortex in both C9+ AFMs and C9+ ALS patients. Interpretation: In asymptomatic C9orf72 repeat expansion carriers, brain MRI reveals widespread features suggestive of impaired neurodevelopment, along with faster decline of motor and parietal cortex than found in normal aging. C9orf72 expression might play a role in cortical development, and consequently explain the specific brain abnormalities of mutation carriers.

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Section: Methodsmentioning

confidence: 99%