Infectious agents, including viruses and bacteria, are proposed to be involved in the pathogenesis of Alzheimer’s disease (AD). According to this hypothesis, these agents have capacity to evade the host immune system leading to chronic infection, inflammation, and subsequent deposition of Aβ and phosphorylated-tau in the brain. Co-existing proteinopathies and age-related pathologies are common in AD and the brains of elderly individuals, but whether these are also related to neuroinfections remain to be established. This study determined the prevalence and distribution of neurodegenerative proteinopathies in patients with infection-induced acute or chronic inflammation associated with herpes simplex virus (HSV) encephalitis (n = 13) and neurosyphilis (n = 23). The mean age at death in HSV patients was 53 ± 12 years (range 24–65 years) and survival was 9 days–6 years following initial infection. The mean age at death and survival in neurosyphilis patients was 60 ± 15 years (range 36–86 years) and 1–5 years, respectively. Neuronal tau-immunoreactivity and neurites were observed in 8 HSV patients and 19 neurosyphilis patients, and in approximately half of these, this was found in regions associated with inflammation and expanding beyond regions expected from the Braak stage of neurofibrillary degeneration. Five neurosyphilis patients had cortical ageing-related tau astrogliopathy. Aβ-plaques were found in 4 HSV patients and 11 neurosyphilis patients. Lewy bodies were observed in one HSV patient and two neurosyphilis patients. TDP-43 pathology was absent. These observations provide insights into deposition of neurodegenerative proteins in neuroinfections, which might have implications for COVID-19 patients with chronic and/or post-infectious neurological symptoms and encephalitis.

包括病毒和细菌在内的传染因子被认为与阿尔茨海默病 (AD) 的发病机制有关。根据这一假设，这些药物具有逃避宿主免疫系统的能力，导致慢性感染、炎症以及随后 Aβ 和磷酸化 tau 在大脑中的沉积。共存的蛋白质病和与年龄相关的病理在 AD 和老年人的大脑中很常见，但这些是否也与神经感染有关仍有待确定。本研究确定了感染引起的与单纯疱疹病毒 (HSV) 脑炎 ( n  = 13) 和神经梅毒 ( n = 23）。HSV 患者的平均死亡年龄为 53 ± 12 岁（范围 24-65 岁），初始感染后的生存期为 9 天-6 年。神经梅毒患者死亡和存活的平均年龄分别为 60±15 岁（范围 36-86 岁）和 1-5 岁。在 8 名 HSV 患者和 19 名神经梅毒患者中观察到神经元 tau 免疫反应性和神经突，其中大约一半发现在与炎症相关的区域，并扩展到神经原纤维变性 Braak 阶段预期的区域之外。五名神经梅毒患者患有皮质衰老相关的 tau 星形胶质细胞病变。在 4 名 HSV 患者和 11 名神经梅毒患者中发现了 Aβ 斑块。在一名 HSV 患者和两名神经梅毒患者中观察到路易小体。不存在 TDP-43 病理。