Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Alzheimers Dement. 2024 Apr;20(4):2894-2905. doi: 10.1002/alz.13711. Epub 2024 Mar 23.
Tau aggregation into paired helical filaments and neurofibrillary tangles is characteristic of Alzheimer's disease (AD) and related disorders. However, biochemical assays for the quantification of soluble, earlier-stage tau aggregates are lacking. We describe an immunoassay that is selective for tau oligomers and related soluble aggregates over monomers.
A homogeneous (single-antibody) immunoassay was developed using a novel anti-tau monoclonal antibody and validated with recombinant and brain tissue-derived tau.
The assay signals were concentration dependent for recombinant tau aggregates in solution but not monomers, and recognized peptides within, but not outside, the aggregation-prone microtubule binding region. The signals in inferior and middle frontal cortical tissue homogenates increased with neuropathologically determined Braak staging, and were higher in insoluble than soluble homogenized brain fractions. Autopsy-verified AD gave stronger signals than other neurodegenerative diseases.
The quantitative oligomer/soluble aggregate-specific assay can identify soluble tau aggregates, including oligomers, from monomers in human and in vitro biospecimens.
The aggregation of tau to form fibrils and neurofibrillary tangles is a key feature of Alzheimer's disease. However, biochemical assays for the quantification of oligomers/soluble aggregated forms of tau are lacking. We developed a new assay that preferentially binds to soluble tau aggregates, including oligomers and fibrils, versus monomers. The assay signal increased corresponding to the total protein content, Braak staging, and insolubility of the sequentially homogenized brain tissue fractions in an autopsy-verified cohort. The assay recognized tau peptides containing the microtubule binding region but not those covering the N- or C-terminal regions only.
tau 蛋白聚集成配对螺旋丝和神经原纤维缠结是阿尔茨海默病（AD）和相关疾病的特征。然而，用于定量可溶性、早期 tau 聚集物的生化检测方法仍然缺乏。我们描述了一种针对 tau 低聚物和相关可溶性聚集物而非单体的免疫测定法。
使用新型抗 tau 单克隆抗体开发了一种均相（单抗体）免疫测定法，并使用重组和脑组织衍生的 tau 进行了验证。
该测定法的信号与溶液中重组 tau 聚集物的浓度呈依赖性，但与单体无关，并且仅识别聚集倾向微管结合区域内而非外的肽段。在中下额额皮质组织匀浆物中，信号随神经病理学确定的 Braak 分期而增加，并且在不溶性比可溶性匀浆脑部分中更高。尸检证实的 AD 比其他神经退行性疾病产生更强的信号。
定量寡聚体/可溶性聚集物特异性测定法可从人源和体外生物样本中鉴定出可溶性 tau 聚集物，包括寡聚体。
tau 蛋白聚集形成纤维和神经原纤维缠结是阿尔茨海默病的一个关键特征。然而，用于定量寡聚体/可溶性 tau 聚集物形式的生化检测方法仍然缺乏。我们开发了一种新的测定法，该测定法优先结合可溶性 tau 聚集物，包括寡聚体和纤维，而非单体。该测定法的信号与总蛋白含量、Braak 分期以及依次匀浆的脑组织部分的不溶性呈正相关。该测定法识别包含微管结合区的 tau 肽段，但不识别仅覆盖 N-或 C-末端区的肽段。
