Department of Neurobiology and Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, AZ, 85013, USA.
Banner Alzheimer's Institute, Phoenix, AZ, USA.
J Neuroinflammation. 2020 Feb 17;17(1):58. doi: 10.1186/s12974-020-1723-x.
Chitinase 3-like 1 (CHI3L1), chitinase 3-like 2 (CHI3L2), and neuronal pentraxin II (NPTX2) are inflammatory biomarkers of Alzheimer's disease (AD). Although studies have demonstrated that cerebrospinal fluid levels of these proteins are changed in AD, no studies have undertaken a detailed examination of alterations in protein levels, cellular expression, and interaction with amyloid in the brain during the progression of AD.
The study evaluated levels of both CHI3L1 and CHI3L2, NPTX2, ionized calcium-binding adapter molecule 1 (Iba1), complement component 1q (C1q), glial fibrillary acidic protein (GFAP), and CD44, in the frontal cortex of people who died with an antemortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD (mAD), and severe AD (sAD) using immunoblot and immunohistochemical techniques.
CHI3L1-immunoreactive (-ir) astrocyte numbers were increased in the frontal cortex and white matter in sAD compared to NCI. On the other hand, increases in GFAP and Iba1-ir cell numbers were observed in MCI compared to NCI but only in white matter. Western blot analyses revealed significantly lower frontal cortex CHI3L2 levels, whereas CD44 levels were increased in sAD. No significant differences for CHI3L1, GFAP, C1q, and NPTX2 protein levels were detected between clinical groups. Strong significant correlations were found between frontal cortex CHI3L1 and Iba1-ir cell numbers in white matter and CHI3L1 and C1q protein levels in the early stages of the disease. C1q and Iba1, CD44 with CHI3L2, and GFAP protein levels were associated during disease progression. CHI3L1 and Iba1 cell numbers in white matter showed a significant associations with episodic memory and perceptual speed.
White matter CHI3L1 inflammatory response is associated with cognitive impairment early in the onset of AD.
几丁质酶 3 样蛋白 1（CHI3L1）、几丁质酶 3 样蛋白 2（CHI3L2）和神经元五肽素 II（NPTX2）是阿尔茨海默病（AD）的炎症生物标志物。尽管研究表明这些蛋白质的脑脊液水平在 AD 中发生了变化，但尚无研究详细检查 AD 进展过程中大脑中蛋白质水平、细胞表达和与淀粉样蛋白相互作用的变化。
该研究使用免疫印迹和免疫组织化学技术评估了死于无认知障碍（NCI）、轻度认知障碍（MCI）、轻度/中度 AD（mAD）和重度 AD（sAD）的患者额皮质中 CHI3L1 和 CHI3L2、NPTX2、离子钙结合衔接蛋白 1（Iba1）、补体成分 1q（C1q）、神经胶质纤维酸性蛋白（GFAP）和 CD44 的水平。
与 NCI 相比，sAD 患者额皮质和白质中的 CHI3L1 免疫反应性（-ir）星形胶质细胞数量增加。另一方面，与 NCI 相比，MCI 患者的 GFAP 和 Iba1-ir 细胞数量增加，但仅在白质中增加。Western blot 分析显示，额叶皮质 CHI3L2 水平显著降低，而 sAD 中 CD44 水平升高。临床组之间未检测到 CHI3L1、GFAP、C1q 和 NPTX2 蛋白水平的显著差异。在疾病的早期阶段，额叶皮质 CHI3L1 与白质中的 Iba1-ir 细胞数量以及 CHI3L1 与 C1q 蛋白水平之间存在强烈的显著相关性。C1q 和 Iba1、CD44 与 CHI3L2 以及 GFAP 蛋白水平在疾病进展过程中相关。白质中 CHI3L1 和 Iba1 细胞数量与情景记忆和知觉速度显著相关。
AD 发病早期，白质 CHI3L1 炎症反应与认知障碍有关。
