PDF(Pubmed)
Abstract：
This case documents the co-occurrence of the fragile X-associated tremor ataxia syndrome (FXTAS) and Alzheimer-type neuropathology in a 71-year-old premutation carrier with 85 CGG repeats in the fragile X mental retardation 1 (FMR1) gene, in addition to an apolipoprotein E (APOE) ε4 allele. FXTAS and Alzheimer\'s Disease (AD) are late-onset neurodegenerative diseases that share overlapping cognitive deficits including processing speed, working memory and executive function. The prevalence of coexistent FXTAS-AD pathology remains unknown. The clinical picture in this case was marked with rapid cognitive decline between age 67 and 71 years in addition to remarkable MRI changes. Over the 16 months between the two clinical evaluations, the brain atrophied 4.12% while the lateral ventricles increased 26.4% and white matter hyperintensities (WMH) volume increased 15.6%. Other regions atrophied substantially faster than the whole brain included the thalamus (-6.28%), globus pallidus (-10.95%), hippocampus (-6.95%), and amygdala (-7.58%). A detailed postmortem assessment included an MRI with confluent WMH and evidence of cerebral microbleeds (CMB). The histopathological study demonstrated FXTAS inclusions in neurons and astrocytes, a widespread presence of phosphorylated tau protein and, amyloid β plaques in cortical areas and the hippocampus. CMBs were noticed in the precentral gyrus, middle temporal gyrus, visual cortex, and brainstem. There were high amounts of iron deposits in the globus pallidus and the putamen consistent with MRI findings. We hypothesize that coexistent FXTAS-AD neuropathology contributed to the steep decline in cognitive abilities.
摘要：
该病例记录了脆性X相关震颤共济失调综合征（FXTAS）和阿尔茨海默型神经病理学在71岁的前突变携带者中的共同发生，在脆性X智力低下1（FMR1）基因中具有85个CGG重复，除了载脂蛋白E（APOE）ε4等位基因。FXTAS和阿尔茨海默病（AD）是迟发性神经退行性疾病，具有重叠的认知缺陷，包括处理速度，工作记忆和执行功能。共存的FXTAS-AD病理的患病率仍然未知。在这种情况下，除了显着的MRI变化外，临床表现在67至71岁之间还具有快速的认知能力下降。在两次临床评估之间的16个月中，大脑萎缩4.12％，而侧脑室增加26.4％，白质高信号（WMH）体积增加15.6％。其他区域萎缩的速度大大超过整个大脑包括丘脑（-6.28％），苍白球（-10.95%），海马（-6.95%），和杏仁核(-7.58%)。详细的验尸评估包括具有融合WMH的MRI和脑微出血（CMB）的证据。组织病理学研究表明，FXTAS在神经元和星形胶质细胞中包含，磷酸化tau蛋白的广泛存在，皮质区和海马中的淀粉样蛋白β斑块。在中央前回注意到CMBs，颞中回,视觉皮层,和脑干。与MRI发现一致，苍白球和壳核中有大量的铁沉积物。我们假设共存的FXTAS-AD神经病理学导致认知能力急剧下降。
