The amyloid cascade hypothesis states that Aβ aggregates induce pathological changes in tau, leading to neurofibrillary tangles (NFTs) and cell death. A caveat with this hypothesis is the spatio-temporal divide between plaques and NFTs. This has been addressed by the inclusion of soluble Aβ and tau species in the revised amyloid cascade hypothesis. Nevertheless, despite the potential for non-plaque Aβ to contribute to tau pathology, few studies have examined relative correlative strengths between total Aβ, plaque Aβ and intracellular Aβ with tau pathology within a single tissue cohort. Employing frozen and fixed frontal cortex grey and white matter tissue from non-AD controls (Con; n = 39) and Alzheimer’s disease (AD) cases (n = 21), biochemical and immunohistochemical (IHC) measures of Aβ and AT-8 phosphorylated tau were assessed. Biochemical native-state dot blots from crude tissue lysates demonstrated robust correlations between total Aβ and AT-8 tau, when considered as a combined cohort (Con and AD) and when as Con and AD cases, separately. In contrast, no associations between Aβ plaques and AT-8 were reported when using IHC measurements in either Con or AD cases. However, when intracellular Aβ was measured via the Aβ specific antibody MOAB-2, a correlative relationship with AT-8 tau was reported in non-AD controls but not in AD cases. Collectively the data suggests that accumulating intracellular Aβ may influence AT-8 pathology, early in AD-related neuropathological change. Despite the lower levels of phospho-tau and Aβ in controls, the robust correlative relationships observed suggest a physiological association of Aβ production and tau phosphorylation, which may be modified during disease. This study is supportive of a revised amyloid cascade hypothesis and demonstrates regional associative relationships between tau pathology and intracellular Aβ, but not extracellular Aβ plaques.

淀粉样蛋白级联假说指出，Aβ 聚集会诱导 tau 蛋白发生病理变化，导致神经原纤维缠结 (NFT) 和细胞死亡。这一假设的一个警告是斑块和 NFT 之间的时空鸿沟。通过将可溶性 Aβ 和 tau 蛋白纳入修订后的淀粉样蛋白级联假说中，这一问题得到了解决。然而，尽管非斑块 Aβ 可能有助于 tau 病理学，但很少有研究检查单个组织队列中总 Aβ、斑块 Aβ 和细胞内 Aβ 与 tau 病理学之间的相对相关强度。采用来自非 AD 对照 (Con；n  = 39) 和阿尔茨海默病 (AD) 病例 ( n  = 21) 的冷冻和固定额叶皮质灰质和白质组织，对 Aβ 和 AT-8 磷酸化进行生化和免疫组织化学 (IHC) 测量tau 进行了评估。来自粗组织裂解物的生化天然状态点印迹显示，当被视为组合队列（Con 和 AD）以及单独被视为 Con 和 AD 病例时，总 Aβ 和 AT-8 tau 之间存在强大的相关性。相比之下，在 Con 或 AD 病例中使用 IHC 测量时，没有报告 Aβ 斑块与 AT-8 之间存在关联。然而，当通过 Aβ 特异性抗体 MOAB-2 测量细胞内 Aβ 时，在非 AD 对照中报告了与 AT-8 tau 的相关关系，但在 AD 病例中却没有报告。总的来说，数据表明，细胞内 Aβ 的积累可能会影响 AT-8 病理学，在 AD 相关神经病理学变化的早期。尽管对照组的磷酸化 tau 和 Aβ 水平较低，但观察到的强有力的相关关系表明 Aβ 产生和 tau 磷酸化之间存在生理关联，这种关联可能在疾病期间发生改变。这项研究支持修订后的淀粉样蛋白级联假说，并证明了 tau 病理学与细胞内 Aβ 之间的区域关联关系，但与细胞外 Aβ 斑块无关。