Fu Hualin, Li Jilong, Zhang Chunlei, Gao Guo, Ge Qiqi, Guan Xinping, Cui Daxiang
Institute of Nano Biomedicine and Engineering, School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Institute of Marine Equipment, Shanghai Jiao Tong University, Shanghai, China.
Neural Regen Res. 2026 Feb 1;21(2):790-799. doi: 10.4103/NRR.NRR-D-24-01440. Epub 2024 Apr 30.
JOURNAL/nrgr/04.03/01300535-202602000-00047/figure1/v/2025-05-05T160104Z/r/image-tiff Alzheimer's disease is a multi-amyloidosis disease characterized by amyloid-β deposits in brain blood vessels, microaneurysms, and senile plaques. How amyloid-β deposition affects axon pathology has not been examined extensively. We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer's disease patients. Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer's disease. On average, amyloid-β-positive axon diameters in Alzheimer's disease brains were 1.72 times those of control brain axons. Furthermore, axonal amyloidosis was associated with microtubule-associated protein 2 reduction, tau phosphorylation, lysosome destabilization, and several blood-related markers, such as apolipoprotein E, alpha-hemoglobin, glycosylated hemoglobin type A1C, and hemin. Lysosome destabilization in Alzheimer's disease was also clearly identified in the neuronal soma, where it was associated with the co-expression of amyloid-β, Cathepsin D, alpha-hemoglobin, actin alpha 2, and collagen type IV. This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability. Additionally, the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes. Furthermore, under rare conditions, axonal breakages were observed, which likely resulted in Wallerian degeneration. In summary, axonal enlargement associated with amyloidosis, micro-bleeding, and lysosome destabilization is a major defect in patients with Alzheimer's disease. This finding suggests that, in addition to the well-documented neural soma and synaptic damage, axonal damage is a key component of neuronal defects in Alzheimer's disease.
《期刊》/nrgr/04.03/01300535 - 202602000 - 00047/图1/v/2025 - 05 - 05T160104Z/图像 - tiff 阿尔茨海默病是一种多淀粉样变性疾病，其特征为脑血管中存在淀粉样β沉积、微动脉瘤和老年斑。淀粉样β沉积如何影响轴突病理尚未得到广泛研究。我们使用免疫组织化学和免疫荧光染色来分析阿尔茨海默病患者的前脑组织切片。在阿尔茨海默病患者中观察到广泛的轴突淀粉样变性，并伴有明显的轴突肿大。平均而言，阿尔茨海默病大脑中淀粉样β阳性轴突直径是对照脑轴突的1.72倍。此外，轴突淀粉样变性与微管相关蛋白2减少、tau蛋白磷酸化、溶酶体不稳定以及几种血液相关标志物有关，如载脂蛋白E、α - 血红蛋白、糖化血红蛋白A1C和血红素。在神经元胞体中也明确鉴定出阿尔茨海默病中的溶酶体不稳定，它与淀粉样β、组织蛋白酶D、α - 血红蛋白、肌动蛋白α2和IV型胶原的共表达有关。这表明外源性出血性蛋白摄入会影响神经溶酶体稳定性。此外，数据显示含淀粉样β的溶酶体比对照溶酶体大2.23倍。此外，在罕见情况下，观察到轴突断裂，这可能导致华勒氏变性。总之，与淀粉样变性、微出血和溶酶体不稳定相关的轴突肿大是阿尔茨海默病患者的一个主要缺陷。这一发现表明，除了有充分记录的神经胞体和突触损伤外，轴突损伤是阿尔茨海默病神经元缺陷的一个关键组成部分。
