The T allele in rs1768208 located in or near the myelin oligodendrocyte basic protein gene (MOBP) is a risk factor for frontotemporal degeneration pathology. We evaluated the hypothesis that the presence of a T allele in rs1768208 will be associated with rate of cognitive decline in behavioral variant frontotemporal degeneration (bvFTD) related to compromised frontal networks. We studied 81 individuals clinically diagnosed with bvFTD who were genotyped for rs1768208 and coded using a dominant model reflecting the presence (i.e., MOBP +) or absence (MOBP −) of the T risk allele. Linear mixed-effects models assessed the association of genotype on neuropsychological performance over time. Regression analyses examined differences in network structure by MOBP genotype. We found a genotype by time interaction for declining cognitive performance, whereby MOBP + individuals demonstrated faster rates of decline in executive function. The presence of a MOBP risk allele was associated with degradation of white matter network features in the frontal lobe. These findings suggest that individual genetic variation may contribute to heterogeneity in clinical progression.

位于或靠近髓鞘少突胶质细胞碱性蛋白基因 ( MOBP)的 rs1768208 中的 T 等位基因是额颞叶退化病理学的危险因素。我们评估了一个假设，即 rs1768208 中 T 等位基因的存在将与额叶网络受损相关的行为变异额颞叶退化 (bvFTD) 的认知下降率相关。我们研究了 81 名临床诊断为 bvFTD 的个体，他们针对 rs1768208 进行了基因分型，并使用反映存在（即MOBP +）或不存在（MOBP - ）的显性模型进行编码T 风险等位基因。线性混合效应模型评估了基因型与神经心理学表现随时间的关联。回归分析通过 MOBP 基因型检查了网络结构的差异。我们通过时间相互作用发现了认知能力下降的基因型，由此MOBP +个体表现出更快的执行功能下降速度。MOBP风险等位基因的存在与额叶中白质网络特征的退化有关。这些发现表明个体遗传变异可能导致临床进展的异质性。