COVID-19 related inflammation as a risk factor for age-related cognitive decline and Alzheimer's Disease

COVID-19 相关炎症是与年龄相关的认知能力下降和阿尔茨海默病的危险因素

基本信息

批准号：
10646590
负责人：
Natalie Celia Tronson
金额：
$ 23.4万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10646590
关键词：
2019-nCoV APP-PS1 Acceleration Adult Age-associated memory impairment Aging Agonist Alzheimer like pathology Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Behavioral Brain COVID-19 COVID-19 impact COVID-19 pandemic COVID-19 survivors Data Dementia Disease Progression Female Future Gene Expression Profiling Genotype Goals Hippocampus Immune Immune signaling Impaired cognition Individual Inflammation Inflammatory Injury Interferon Type I Knowledge Laboratories Lipopolysaccharides Long COVID Long-Term Effects Mediating Memory Memory Disorders Memory Loss Memory impairment Microglia Molecular Analysis Mus Nerve Degeneration Neuroimmune Neuroimmunomodulation Neuronal Plasticity Pathway interactions Persons Play Population Prevention strategy Preventive treatment Process Protein Biochemistry Protocols documentation RNA Viruses Recovery Reporting Research Resolution Risk Risk Factors Risk Reduction Role Senile Plaques Sex Differences Signal Transduction Survivors Symptoms TLR3 gene TLR4 gene TLR7 gene TLR8 gene Testing Time Transgenic Mice Virus Wild Type Mouse Woman Work age related behavior test beta amyloid pathology chemokine cognitive function coronavirus disease cytokine dementia risk immune activation male middle age mouse model neuroinflammation novel pandemic disease post-COVID-19 sex tau aggregation young adult

项目摘要

PROJECT SUMMARY More than 85 million cases of COVID-19 have been recorded in the US alone, and up to 40% of survivors report Long-COVID symptoms including cognitive impairments. Together with evidence that inflammation during adulthood increases risk for later cognitive decline, this raises the prospect that the COVID-19 pandemic will cause a future “second pandemic” in Alzheimer’s disease and age-related dementias. In this project, we will identify specific mechanisms by which single stranded RNA (ssRNA) viruses (e.g., SARS-COV- 2) triggered innate immune signaling contributes to long-lasting memory impairments, exaggerated cognitive decline during aging, and risk for dementias including Alzheimer’s disease. Our main goal is to determine the impact of innate immune signaling as a consequence of ssRNA viruses on exaggeration of age-related cognitive decline and risk for dementias including Alzheimer’s Disease. We will use a subchronic inflammation protocol, established in my laboratory, together with behavioral tests of memory, protein biochemistry, and gene expression assays to identify persistent changes in inflammatory state and neuroplasticity mechanisms that exacerbate cognitive decline. We will use wild-type mice and APP/PS1 transgenic mice to determine whether TLR7-induced inflammation causes acceleration of age-related cognitive decline and AD-like pathology. Findings from this project will demonstrate how COVID-19, and other TLR7-induced inflammation increases risk for dementia; identify sex differences in COVID-related vulnerability to cognitive decline; and provide a basis for novel preventive strategies and treatments to reduce risk for Alzheimer’s disease and other dementias in the post-COVID-19 population.

项目摘要仅在美国，就已经记录了超过8500万例Covid-19案件，最多40％的幸存者报告长舒联症状，包括认知障碍。以及炎症的证据在成年期间增加了后来认知能力下降的风险，这提高了Covid-19的前景大流行将在阿尔茨海默氏病和与年龄有关的痴呆症中引起未来的“第二大流行”。在这个项目，我们将确定单个链RNA（SSRNA）病毒（例如SARS-COV-）的特定机制 2）触发先天免疫信号传导有助于长期记忆障碍，夸张的认知衰老期间的下降以及包括阿尔茨海默氏病在内的痴呆症风险。我们的主要目标是确定 ssRNA病毒对先天免疫信号传导的影响对年龄相关的夸张包括阿尔茨海默氏病在内的痴呆症的认知能力下降和风险。我们将使用亚慢性炎症协议，在我的实验室中建立，以及记忆，蛋白质生物化学和基因表达分析以识别炎症状态和神经塑性机制的持续变化这种加剧的认知能力下降。我们将使用野生型小鼠和App/ps1转基因小鼠来确定 TLR7诱导的炎症是否会导致与年龄相关的认知下降和类似AD的加速病理。该项目的发现将证明COVID-19和其他TLR7诱导的炎症如何增加痴呆症的风险；确定与认知下降的脆弱性相关脆弱性的性别差异；和为新颖的预防策略和治疗提供了基础，以降低阿尔茨海默氏病和其他的风险 199年后人口的痴呆症。