Gut microbiome and blood indices in patients with AD and their spousal caregivers

AD 患者及其配偶照顾者的肠道微生物组和血液指数

• 批准号: 10575244
• 负责人: Patrick Finan
• 金额: $ 24.23万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10575244
• 关键词: Acceleration; Acetates; Address; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease caregiver; Alzheimer' s disease patient; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein Precursor; Animals; Antiinflammatory Effect; Attenuated; Biological Markers; Blood; Brain; Caregivers; Cognition; Cognitive; Data; Dementia; Dementia caregivers; Development; Disease; Disease Outcome; Elderly; Environment; Event; Functional disorder; Health; Healthcare; Human; Impaired cognition; Impairment; Inflammation; Inflammatory; Inflammatory Response; Knowledge; Learning; Life; Mediator; Memory; Memory impairment; Mus; Neurofibrillary Tangles; Neuronal Injury; Operative Surgical Procedures; Participant; Partner in relationship; Pathologic; Pathologic Processes; Patient Care; Patients; Positron-Emission Tomography; Reporting; Role; Senile Plaques; Spouse Caregiver; Spouses; Stress; Time; Volatile Fatty Acids; Wild Type Mouse; amyloid peptide; biomarker identification; caregiving; cytokine; dementia risk; extracellular; gut bacteria; gut dysbiosis; gut microbiome; gut microbiota; high risk; hyperphosphorylated tau; improved; indexing; microbiome alteration; n-pentanoic acid; neuroinflammation; neuropathology; neurotoxicity; potential biomarker; preclinical study; recruit; tau Proteins

Patients with Alzheimer’s disease (AD) have gut dysbiosis. Short chain fatty acids (SCFAs) are products of gut microbiome. Among them, Acetate and valeric acid were found to be positively correlated with the Aβ plaque load detected by amyloid PET in participants with or without AD. However, the levels of SCFAs in the blood of patients with AD have not been defined. Also, the usefulness of indices of inflammation and neuropathology in the blood as biomarkers for cognitive impairment in patients with AD is elusive. Importantly, spousal caregivers of patients with dementia have a higher risk of developing dementia later in life than those whose spouses do not have dementia. The spousal caregivers have an accelerated cognitive decline. The mechanisms for these phenomena are not known. We hypothesize that spousal caregivers of patients with AD have gut microbiome and levels of blood SCFAs similar to those of patients with AD, that these spouses have increased inflammatory cytokines and indices of AD-like neuropathology in the blood, and that there is a correlation between the cognition and various indices in the blood among patients with AD, their spouses and age- matched controls. To address these hypotheses, we will recruit three groups of participants: patients with AD, their spousal caregivers and controls that are age-matched with the caregivers. Their gut microbiome and indices of neuroinflammation and neuropathology in the blood will be determined. Their cognition will be assessed. The correction of cognition with gut microbiome genera or indices in the blood will be analyzed. Our studies may represent first study to determine whether gut microbiome and SCFAs may play a role in the cognitive impairment in the spousal caregivers of patients with AD. These studies may also identify biomarkers for cognitive impairment in these caregivers and patients with AD. These findings may ultimately help the care of patients with AD and reduce the cognitive declines in spousal caregivers of patients with AD.

阿尔茨海默病(AD)患者有肠道生物失调。短链脂肪酸 单链脂肪酸(SCFA)是肠道微生物群的产物。其中，醋酸盐和戊酸被发现 与A-β斑块负荷呈正相关 没有AD。然而，阿尔茨海默病患者血液中的单链脂肪酸水平尚未达到 已定义。此外，血液中炎症和神经病理指标的有用性 阿尔茨海默病患者认知障碍的生物标志物还很难捉摸。重要的是，配偶 痴呆症患者的照顾者在晚年患痴呆症的风险比 配偶没有患痴呆症的人。配偶照顾者有一个加速的 认知能力下降。这些现象的机制尚不清楚。我们假设 AD患者的配偶照顾者肠道微生物群和血液中SCFAs水平相似 对于AD患者来说，这些配偶的炎性细胞因子和 血液中的AD样神经病理指标，并且在 阿尔茨海默病患者及其配偶、年龄与认知及血液各项指标的关系 配对的对照组。为了解决这些假设，我们将招募三组参与者： AD患者，他们的配偶照顾者和与年龄匹配的对照组 照顾者。他们的肠道微生物群以及神经炎症和神经病理指标 血液将会被确定。他们的认知能力将被评估。用直觉纠正认识 将对血液中的微生物组属或指标进行分析。我们的研究可能代表了第一个 确定肠道微生物组和单链脂肪酸是否可能在认知中起作用的研究 阿尔茨海默病患者配偶照顾者的损害。这些研究还可能确定 这些照顾者和AD患者认知障碍的生物标记物。这些发现 可能最终有助于AD患者的护理并减少配偶的认知能力下降 AD患者的照顾者。