Expanding insights into FTD disease mechanisms

摘要 在住院的新冠肺炎患者中，多达三分之二的人出现了神经系统症状和体征。例如，一些 患有新冠肺炎的患者会出现认知变化(或脑雾)或中风和癫痫。它是 假设新冠肺炎引起的脑炎症和脑白质损伤是神经学的基础 新冠肺炎患者的临床表现。因为神经炎和脑白质损伤 新冠肺炎还与阿尔茨海默病相关痴呆(ADRD)有关，可能会增加患 开发ADRD。然而，许多问题仍然得到解答，亚急性和长期的 新冠肺炎对神经系统的影响尚不清楚。因此，我们建议进行全面的纵向 需要住院治疗的新冠肺炎患者的研究。以确定有长期神经系统疾病风险的患者 神经元标记物--血清神经丝轻链(NFL)的水平、并发症和必要的随访 伤情，将在医院测量。我们基于我们最近的发现，在最初的142名队列中，约53%的人 新冠肺炎的住院患者血清神经营养因子水平升高，与神经营养因子浓度的升高相关 临床结果越差，包括需要机械通气、重症监护病房入院时间越长 住院时间长，功能结果差。因此，NFL测量提供了一种有效的手段 评估与急性感染和即将到来的全身代谢相关的神经损伤的程度 骚乱。我们将在出院后3个月、1年和2年对同意的患者进行跟踪检查。 神经元和星形胶质细胞损伤的血液生物标记物，ADRD病理和神经炎症，成像标记物 神经炎症和Aβ沉积，以及认知结果。这些数据将使我们能够确定 住院期间血液生物标志物水平预测ADRD相关神经疾病的出现和严重程度 体征和症状。我们还将扩展我们先前的神经病理学研究，用于新冠肺炎和 ADRDS，并评估缺氧缺血性脑白质损伤、神经炎症和小胶质细胞激活。

ABSTRACT Up to two thirds of hospitalized COVID-19 patients show neurologic signs and symptoms. For example, some patients with COVID-19 experience cognitive changes (or brain fog) or suffer strokes and seizures. It is hypothesized that COVID-19-induced brain inflammation and white matter damage underpin the neurological manifestations experienced by patients with COVID-19. Since neuroinflammation and white matter damage are also implicated in Alzheimer’s disease related dementias (ADRDs), COVID-19 may increase the risk of developing an ADRD. Nevertheless, many questions remain answered, and the subacute and long-term neurological effects of COVID-19 are unknown. We thus propose to undertake a comprehensive longitudinal study of patients with COVID-19 requiring hospitalization. To identify patients at risk of long-term neurological complications and warranting follow-up visits, levels of serum neurofilament light chain (NFL), a marker of neuron injury, will be measured in hospital. We based this on our recent findings that ~53% of an initial cohort of 142 hospitalized patients with COVID-19 had elevated serum NFL, and that higher NFL concentrations correlated with worse clinical outcomes, including the need for mechanical ventilation, intensive care unit admission, longer lengths of hospitalization and poor functional outcomes. As such, NFL measurements provide an efficient means to estimate the extent of neurological injury associated with the acute infection and pending systemic metabolic disturbances. We will follow consenting patients 3 months, 1 year and 2 years after discharge, and examine blood biomarkers of neuronal and astroglial injury, ADRD pathologies and neuroinflammation, imaging markers of neuroinflammation and Aβ deposition, and cognitive outcomes. These data will allow us to determine whether blood biomarker levels during hospitalization predict the emergence and severity of ADRD-related neurological signs and symptoms. We will also extend our prior neuropathological studies in patients with COVID-19 and ADRDs, and assess anoxic-ischemic cerebral white matter damage, neuroinflammation and microglial activation.