Division of Neurology, Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
Department of Molecular Genetics, Brain Research Institute, Niigata University, Chuo-ku, Niigata, Japan.
J Alzheimers Dis. 2021;80(2):639-646. doi: 10.3233/JAD-201407.
Toxic amyloid-β protein (Aβ) conformers play an important role in the progression of Alzheimer's disease (AD). The ratio of toxic conformer to total Aβ42 in cerebrospinal fluid (CSF) was significantly high in AD and mild cognitive impairment (MCI) due to AD using an enzyme-linked immunosorbent assay kit with a 24B3 antibody.
We compared the toxic Aβ42, conformer at different stages of AD to identify its contribution to AD pathogenesis.
We compared 5 patients with preclinical AD, 11 patients with MCI due to AD, 21 patients with AD, and 5 healthy controls to measure CSF levels of total Aβ42, total tau, tau phosphorylated at threonine 181 (p-tau), and toxic Aβ conformers. All were classified using the Clinical Dementia Rating. Cognitive function was assessed using the Japanese version of the Mini-Mental State Examination (MMSE-J).
Toxic Aβ conformer level was insignificant between groups, but its ratio to Aβ42 was significantly higher in AD than in preclinical AD (p < 0.05). Toxic Aβ42 conformer correlated positively with p-tau (r = 0.67, p < 0.01) and p-tau correlated negatively with MMSE-J (r = -0.38, p < 0.05).
Toxic Aβ conformer triggers tau accumulation leading to neuronal impairment in AD pathogenesis.
有毒的淀粉样β蛋白（Aβ）构象在阿尔茨海默病（AD）的进展中起着重要作用。使用针对 24B3 抗体的酶联免疫吸附测定试剂盒，AD 和轻度认知障碍（MCI）患者脑脊液（CSF）中总 Aβ42 与毒性 Aβ42 构象的比例明显升高。
我们比较了 AD 不同阶段的有毒 Aβ42 构象，以确定其对 AD 发病机制的贡献。
我们比较了 5 例临床前 AD 患者、11 例 AD 所致 MCI 患者、21 例 AD 患者和 5 例健康对照者，以测量 CSF 中总 Aβ42、总 tau、磷酸化 tau （T181）和有毒 Aβ 构象的水平。所有患者均采用临床痴呆评定量表进行分类。采用简易精神状态检查（MMSE-J）日本版评估认知功能。
各组间有毒 Aβ 构象水平无显著性差异，但 AD 组的比例明显高于临床前 AD 组（p < 0.05）。有毒 Aβ42 构象与 p-tau 呈正相关（r = 0.67，p < 0.01），p-tau 与 MMSE-J 呈负相关（r = -0.38，p < 0.05）。
有毒 Aβ 构象引发 tau 聚集，导致 AD 发病机制中的神经元损伤。
