The current study sought to examine the relative influence of genetic and environmental factors on corpus callosum (CC) microstructure in a community sample of older adult twins. (ii) whole CC DTI steps with total brain WML burden. Across the DTI steps for the whole CC, MD and RD shared 84% of the common genetic variance, followed by MD- AD (77%), FA – RD (52%), RD – AD (37%) and FA C MD (11%). For total WMLs, significant genetic correlations indicated that there was 19% shared common genetic variance with whole CC MD, followed by CC RD (17%), CC AD (16%) and CC FA (5%). Our findings suggest that the CC microstructure is usually under moderate genetic control. There was also evidence Rabbit Polyclonal to TBC1D3 of shared genetic factors between the CC DTI steps. In contrast, there was less shared genetic variance between WMLs and the CC DTI metrics, suggesting fewer common genetic variants. Introduction The corpus callosum (CC) is the largest white matter (WM) tract connecting the two cerebral hemispheres and contains more than 2108 axons [1], [2]. The size and myelination of these fibres determine the time taken for inter-hemispheric transfer of information [3]. Diffusion tensor imaging (DTI) is used to study WM integrity, and it provides quantitative three-dimensional analyses of WM microstructure [4], [5]. Different DTI steps such as anisotropy (fractional anisotropy-FA) and diffusivity (mean diffusivity- MD; radial diffusivity- RD and axial diffusivity- AD) can be obtained, each of which is sensitive to different aspects of WM integrity, including levels of myelination (FA, RD), axonal density/diameter (FA), axonal damage or loss (AD) [6]C[10]. Ageing leads to macro and microstructural changes to fibres in the CC, affecting inter-hemispheric processing [11]. Although the number of fibres in the CC does not Etifoxine hydrochloride IC50 change from birth [12], their size, density [2] and composition (myelination) [12] varies with age [1]. For the CC, greater atrophy using DTI measures has been observed with increasing age in the anterior and mid-body regions compared to posterior regions [5], [13], [14]. Age-related changes in the CC [15], [16] have been associated with age-related cognitive impairment [17]C[19], reduced processing speed [20], bimanual motor decline [21] and neurodegenerative disease [22]C[25]. Moreover, the study of WM integrity measures in Etifoxine hydrochloride IC50 older individuals may help in the early diagnosis of disease such as Alzheimer’s disease and mild cognitive impairment [26]C[28] and may serve as biomarkers to differentiate them at an early stage [29]. Hence, it is important to gain a better understanding of the role of genetic and environmental factors in age-related integrity of the CC. Further, studying the genetics of CC in older individuals may help to understand the aetiology of the age-related degeneration of CC and also clarify the relationship between its microstructure, function and disease. Heritability studies provide evidence for the role of genes in WM integrity [30]. To date, however, the heritability of CC in older individuals has been reported in only two studies, one examining FA in older males only [31], while the other used an extended family study design [32]. In a small sample of older males (n?=?64), the heritability for FA of the CC splenium (67%) was found to be more than that of the genu (49%) [31]. However, in an extended family study (n?=?467), which included older adults (age range 19C85 yrs), heritability of FA across the lifespan for the genu was high (66%), with heritability values of FA for the body of CC and splenium ranging from 54C57%. Also, CC RD was reported to be heritable (37%), but not AD [32]. The heritability of MD was not reported in either of these two studies. Therefore, more Etifoxine hydrochloride IC50 studies are required to examine heritability of all CC DTI measures.