HIV-1 and Alzheimer’s disease: Comorbidity
HIV-1 和阿尔茨海默病:合并症
基本信息
- 批准号:10760712
- 负责人:
- 金额:$ 40.7万
- 依托单位:
- 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:2023-09-01 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAddressAdultAffectAgeAlzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaAmyloidAmyloid beta-ProteinAnimal ModelAreaBehavioralBiochemistryBrainCase StudyCentral Nervous System InfectionsCharacteristicsCognitiveCognitive deficitsDataDementiaDisease ProgressionEconomicsGoalsHIVHIV InfectionsHIV SeropositivityHIV diagnosisHIV-1HIV-associated neurocognitive disorderHealthHumanImpaired cognitionIndividualKnock-in MouseKnowledgeLongitudinal StudiesMedical Care CostsModelingMolecular BiologyMusNeurodegenerative DisordersNeurofibrillary TanglesOnset of illnessOutcomeOutcome MeasurePathologyPersonsPopulationReportingResearchResearch PersonnelSample SizeSenile PlaquesSynapsesTestingTherapeutic StudiesTransgenic MiceTreatment ProtocolsWorld Health Organizationage related neurodegenerationagedantiretroviral therapybiological systemscognitive functioncomorbidityearly onsetinterdisciplinary approachmouse modelnervous system disorderneurodegenerative dementianeuropathologypharmacologicpublic health relevancetau Proteinstool
项目摘要
PROJECT SUMMARY/ABSTRACT
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by a progressive
impairment of cognitive functions.
The World Health Organization estimates that 55 million people worldwide live
with dementia, of which two-thirds are due to AD, and this number is expected to increase to 131.5 million by
2050. In 2021 an estimated 38.4 million people were living with Human immunodeficiency virus-1 (HIV). HIV-
associated neurocognitive disorder (HAND) is a common primary neurological disorder associated with HIV
infection of the central nervous system, despite successful virologic control with combination antiretroviral
therapy (cART). 50% of the US HIV-positive population
is aged 50 years or older, mainly due to the successful
treatment regimens helping HIV-positive adults survive for decades with HIV. There is concern AD may become
prevalent with an earlier onset of cognitive deficit or accelerate the disease progression. Currently, there are no
scientific data to support or oppose if HIV can affect the onset and progression of AD cognitive decline. To
address this critical knowledge gap and test the hypothesis, we will use two AD mouse models, human amyloid
knock-in mouse (hAβKI) and Tau transgenic mice models infected with chimeric HIV (EcoHIV). Our central
hypothesis is that HIV promotes the onset of cognitive decline in AD mice models. We will use a multidisciplinary
approach to test the hypothesis, including behavioral, pharmacological, molecular biology, and biochemistry.
Aim 1. We will perform the first longitudinal studies using 2 AD mouse models, an HIV model that mimics PLWH,
and multiple outcome measures capturing several AD-associated cognitive dysfunctions to determine if EcoHIV
accelerates the onset of cognitive decline in AD mice. We will also explore the potential mechanism (e.g., Aβ
disposition).
This application addresses critical health conditions and a new challenge that looms as individuals living with
HIV age and reach age-related neurodegenerative diseases: HIV and AD comorbidity. A potential outcome will
be that EcoHIV promotes the onset of cognitive decline in AD mice. This knowledge has the potential to advance
the field of HIV and AD comorbidity because it will show that HIV and AD are not independent health conditions,
but when they are comorbid, HIV can interfere with AD cognitive decline onset.
项目总结/摘要
阿尔茨海默病(AD)是一种破坏性的神经退行性疾病,其特征在于进行性的
认知功能受损。
世界卫生组织估计,全世界有5500万人
患有痴呆症的人,其中三分之二是由于AD,预计到2020年,这一数字将增加到1.315亿。
2050. 2021年,估计有3840万人感染人类免疫缺陷病毒1(艾滋病毒)。艾滋病毒-
相关性神经认知障碍(HAND)是一种常见的与HIV相关的原发性神经系统疾病
中枢神经系统感染,尽管联合抗逆转录病毒药物成功控制了病毒
治疗(cART)50%的美国艾滋病毒阳性人口
年龄在50岁或以上,主要是由于成功的
治疗方案帮助艾滋病毒阳性成人存活数十年的艾滋病毒。人们担心AD可能会成为
普遍存在认知缺陷的早期发作或加速疾病进展。目前没有
科学数据来支持或反对艾滋病毒是否会影响AD认知能力下降的发作和进展。到
为了解决这一关键的知识缺口并验证这一假设,我们将使用两种AD小鼠模型,人类淀粉样蛋白
敲入小鼠(hAβKI)和感染嵌合HIV的Tau转基因小鼠模型(EcoHIV)。我们的中央
假设是HIV促进AD小鼠模型中认知下降的发作。我们将使用多学科
检验假说的方法,包括行为学、药理学、分子生物学和生物化学。
目标1。我们将使用2种AD小鼠模型,一种模拟PLWH的HIV模型,
和多个结局指标,捕捉几个AD相关的认知功能障碍,以确定EcoHIV是否
加速AD小鼠认知能力下降的发生。我们还将探讨潜在的机制(例如,Aβ
处置)。
该应用程序解决了关键的健康状况和一个新的挑战,作为个人生活与
艾滋病毒年龄和达到年龄相关的神经退行性疾病:艾滋病毒和AD合并症。一个潜在的结果将
EcoHIV促进了AD小鼠认知能力的下降。这些知识有可能促进
艾滋病毒和AD共病领域,因为它将表明艾滋病毒和AD不是独立的健康状况,
但当它们共病时,HIV可干扰AD认知功能减退的发作。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Khalid Benamar其他文献
Khalid Benamar的其他文献
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{{ truncateString('Khalid Benamar', 18)}}的其他基金
Endocannabinoid system and HIV-related neuropathic pain
内源性大麻素系统和 HIV 相关的神经性疼痛
- 批准号:
10852472 - 财政年份:2023
- 资助金额:
$ 40.7万 - 项目类别:
Endocannabinoid system and HIV-related neuropathic pain
内源性大麻素系统和 HIV 相关的神经性疼痛
- 批准号:
10242327 - 财政年份:2021
- 资助金额:
$ 40.7万 - 项目类别:
Endocannabinoid system and HIV-related neuropathic pain
内源性大麻素系统和 HIV 相关的神经性疼痛
- 批准号:
10436371 - 财政年份:2021
- 资助金额:
$ 40.7万 - 项目类别:
Beta-caryophyllene (BCP) and cannabidiol (CBD) combination: HIV-1 chronic neuropathic pain
β-石竹烯 (BCP) 和大麻二酚 (CBD) 组合:HIV-1 慢性神经性疼痛
- 批准号:
10490249 - 财政年份:2021
- 资助金额:
$ 40.7万 - 项目类别:
Beta-caryophyllene (BCP) and cannabidiol (CBD) combination: HIV-1 chronic neuropathic pain
β-石竹烯 (BCP) 和大麻二酚 (CBD) 组合:HIV-1 慢性神经性疼痛
- 批准号:
10851326 - 财政年份:2021
- 资助金额:
$ 40.7万 - 项目类别:
Beta-caryophyllene and cannabidiol combination: Chronic arthritis pain
β-石竹烯和大麻二酚组合:慢性关节炎疼痛
- 批准号:
10056530 - 财政年份:2020
- 资助金额:
$ 40.7万 - 项目类别:
Chemokine Antagonist, Opioid Medication and HIV gp120
趋化因子拮抗剂、阿片类药物和 HIV gp120
- 批准号:
8266369 - 财政年份:2011
- 资助金额:
$ 40.7万 - 项目类别:
Chemokine Antagonist, Opioid Medication and HIV gp120
趋化因子拮抗剂、阿片类药物和 HIV gp120
- 批准号:
8140920 - 财政年份:2011
- 资助金额:
$ 40.7万 - 项目类别:
Gp120 in the brain and opioid medications: Functional interactions
大脑中的 Gp120 和阿片类药物:功能相互作用
- 批准号:
8034340 - 财政年份:2010
- 资助金额:
$ 40.7万 - 项目类别:
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