INTRODUCTIONThis study investigated the impact of trisomy 21 mosaicism (mT21) on Alzheimer's disease (AD) neuropathology in a well‐characterized clinical case described by Ringman et al.METHODSWe describe AD neuropathology in mT21 including amyloid beta, phosphorylated tau, astrogliosis, microgliosis, α‐synuclein, and TAR DNA‐binding protein 43 (TDP‐43) in cerebral cortex, hippocampal subregions, and amygdala using immunohistochemistry.RESULTSWe observed high AD neuropathologic change with a score of A3B3C3. In addition, there was widespread astrogliosis, cerebral amyloid angiopathy, and perivascular space widening throughout the brain. Lewy bodies and neurites were noted in the amygdala only and no TDP‐43 was observed.DISCUSSIONThe findings in this case report highlight that mT21 is sufficient to induce AD neuropathology and early‐onset dementia.HIGHLIGHTS Trisomy 21 mosaicism (mT21) occurs when three copies of chromosome 21 are present in some but not all somatic cells in an individual. mT21 accounts for ≈ 2% of people diagnosed with Down syndrome (DS). Immunohistochemical identification of amyloid beta, tau, astrocytes, microglia, α‐synuclein, and TAR DNA‐binding protein 43 show that Alzheimer's disease (AD) pathology in mT21 is similar to full trisomy 21. The findings in this case report highlight that mT21 is sufficient to induce AD neuropathology and early‐onset dementia.

中文翻译：

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早发性痴呆病例中 21 三体嵌合体的神经病理学


引言该研究调查了 21 三体嵌合体 （mT21） 对阿尔茨海默病 （AD） 神经病理学的影响，该病例由 Ringman 等人描述。方法我们描述了 mT21 中的 AD 神经病理学，包括淀粉样蛋白 β、磷酸化 tau、星形胶质细胞增生、小胶质细胞增生、α-突触核蛋白和大脑皮层、海马亚区和杏仁核中的 TAR DNA 结合蛋白 43 （TDP-43）。结果我们观察到较高的 AD 神经病理学变化，评分为 A3B3C3。此外，还存在广泛的星形胶质细胞增生、脑淀粉样血管病和整个大脑的血管周围间隙增宽。仅在杏仁核中观察到路易体和神经突，未观察到 TDP-43。讨论本病例报告中的研究结果强调，mT21 足以诱导 AD 神经病理学和早发性痴呆。亮点 21 三体嵌合症 （mT21） 发生在个体的某些但不是全部体细胞中存在 21 号染色体的三个拷贝时。mT21 占被诊断患有唐氏综合症 （DS） 的人≈ 2%。淀粉样蛋白 β、tau、星形胶质细胞、小胶质细胞、α-突触核蛋白和 TAR DNA 结合蛋白 43 的免疫组织化学鉴定表明，mT21 中的阿尔茨海默病 （AD） 病理学与完全三体 21 相似。本病例报告中的研究结果强调，mT21 足以诱导 AD 神经病理学和早发性痴呆。