The definitive diagnosis of Alzheimer’s disease (AD) rests with post-mortem neuropathology despite the advent of more sensitive scanning and the search for reliable biomarkers. Even though the classic neuropathological features of AD have been known for many years, it was only relatively recently that more sensitive immunohistochemistry for amyloid beta (Aβ) and hyperphosphorylated tau (HP-tau) replaced silver-staining techniques. However, immunohistochemistry against these and other proteins has not only allowed a more scientific evaluation of the pathology of AD but also revealed some mimics of HP-tau pathological patterns of AD, including age-related changes, argyrophilic grain disease and chronic traumatic encephalopathy. It also highlighted a number of cases of AD with significant additional pathology including Lewy bodies, phosphorylated TDP-43 (p-TDP-43) positive neuronal cytoplasmic inclusions and vascular pathology. This concomitant pathology can cause a number of challenges including the evaluation of the significance of each pathological entity in the make-up of the clinical symptoms, and the threshold of each individual pathology to cause dementia. It also raises the possibility of underlying common aetiologies. Furthermore, the concomitant pathologies could provide explanations as to the relative failure of clinical trials of anti-Aβ therapy in AD patients.

中文翻译：

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阿尔茨海默氏病的神经病理学诊断-病理模拟物和伴随病理学的挑战。

尽管出现了更为灵敏的扫描方法和寻找可靠的生物标记物，但死后神经病理学仍是对阿尔茨海默氏病（AD）的明确诊断。尽管已知AD的经典神经病理学特征已有很多年，但直到最近，淀粉样蛋白β（Aβ）和高磷酸化tau（HP-tau）的更敏感的免疫组织化学才替代了银染技术。然而，针对这些蛋白和其他蛋白的免疫组织化学不仅允许对AD的病理进行更科学的评估，而且还揭示了HP-tau AD病理模式的一些模拟物，包括与年龄有关的变化，嗜银粒病和慢性创伤性脑病。它还强调了许多AD病例，其中包括路易氏体，磷酸化的TDP-43（p-TDP-43）阳性神经元胞浆内含物和血管病理。这种伴随的病理学可能引起许多挑战，包括评估每种病理学实体在构成临床症状中的重要性以及每种引起痴呆的病理学的阈值。这也增加了潜在的共同病因的可能性。此外，伴随的病理学可以为AD患者抗Aβ疗法临床试验的相对失败提供解释。以及每种导致痴呆的病理学阈值。这也增加了潜在的共同病因的可能性。此外，伴随的病理学可以为AD患者抗Aβ疗法临床试验的相对失败提供解释。以及每种导致痴呆的病理学阈值。这也增加了潜在的共同病因的可能性。此外，伴随的病理学可以为AD患者抗Aβ疗法临床试验的相对失败提供解释。