Neurite density is reduced in the presymptomatic phase of C9orf72 disease


This paper compared the sensitiviy and specificity between Neurite orientation dispersion and density imaging (NODDI) and conventional techniques, such as Diffusion tensor imaing (DTI) and anatomical MRI, for detecting neuroimaging-based biomarker of C9orf72 mutation presymptomatic carriers. Compared with normal control subjects (C9−), presymptomatic subjects (C9+) demonstrated white matter abnormalities in 10 tracts with neurite density index and only 5 tracts with DTI metrics. effect size was signi cantly higher for the neurite density index than for DTI metrics in two tracts. No tract had a signi cantly higher effect size for DTI than for NODDI. For grey matter cortical analysis, free water fraction was increased in 13 regions in C9+, whereas 11 regions displayed volumetric atrophy. NODDI provides higher sensitivity and greater tissue speci city compared with conventional DTI for identifying white matter abnormalities in the presymptomatic C9orf72 carriers. Our results encourage the use of neurite density as a biomarker of the preclinical phase.

In Journal of Neurology, Neurosurgery, and Psychiatry