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.

项目概要仅在美国就记录了超过 8500 万例 COVID-19 病例，其中高达 40% 的幸存者报告长期新冠病毒症状，包括认知障碍以及炎症证据。在成年期会增加以后认知能力下降的风险，这增加了 COVID-19 的可能性大流行将导致未来的阿尔茨海默病和与年龄相关的痴呆症的“第二次大流行”。项目中，我们将确定单链 RNA (ssRNA) 病毒（例如 SARS-COV- 2）触发先天免疫信号导致长期记忆障碍、过度认知衰老过程中的衰退以及患痴呆症（包括阿尔茨海默病）的风险。 ssRNA 病毒导致的先天免疫信号对年龄相关性夸大的影响认知能力下降和痴呆症（包括阿尔茨海默病）的风险我们将使用亚慢性炎症。在我的实验室建立的协议，以及记忆、蛋白质生物化学和行为测试基因表达测定以确定炎症状态和神经可塑性机制的持续变化我们将使用野生型小鼠和 APP/PS1 转基因小鼠来确定。 TLR7诱导的炎症是否会加速与年龄相关的认知能力下降和AD样症状该项目的研究结果将证明 COVID-19 和其他 TLR7 是如何引起炎症的。增加患痴呆症的风险；确定与新冠病毒相关的认知能力下降的性别差异；以及为新的预防策略和治疗方法提供基础，以降低阿尔茨海默病和其他疾病的风险 COVID-19 后人群中的痴呆症。