Nasu-Hakola disease is a rare autosomal recessive disorder associated to mutations in TREM2 and DAP12 genes, neuropathologically characterized by leukoencephalopathy with axonal spheroids. We report the neuropathologic findings of a 51-year-old female with a homozygous mutation (Q33X) of TREM2 gene. Beside severe cerebral atrophy and hallmarks of Nasu-Hakola disease, significant Alzheimer’s disease lesions were present. Neurofibrillary changes showed an atypical topographic distribution being severe at spots in the neocortex while sparing the mesial temporal structures. Our finding suggests that TREM2 genetic defects may favor Alzheimer’s disease pathology with neurofibrillary changes not following the hierarchical staging of cortical involvement identified by Braak.

中文翻译：

---

具有 TREM2 突变的 Nasu-Hakola 病神经病理性阿尔茨海默病病变：神经原纤维变化的非典型分布

那须-哈科拉病是一种罕见的常染色体隐性遗传病，与 TREM2 和 DAP12 基因突变相关，神经病理学特征为伴有轴突球体的白质脑病。我们报告了一名 51 岁女性具有 TREM2 基因纯合突变 (Q33X) 的神经病理学发现。除了严重的脑萎缩和那须-哈科拉病的标志外，还存在显着的阿尔茨海默病病变。神经原纤维变化显示出在新皮质中的点处严重的非典型地形分布，同时保留了内侧颞叶结构。我们的发现表明，TREM2 遗传缺陷可能有利于阿尔茨海默病病理学，其神经原纤维变化不遵循 Braak 确定的皮质受累的分级分期。