Do Atmospheric Ultrafine Particles Lodge in the Brain and Cause Cognitive Decline Leading to Alzheimer's Disease Related Dementias?

大气超细颗粒是否会滞留在大脑中并导致认知能力下降,从而导致阿尔茨海默病相关的痴呆症?

基本信息

  • 批准号:
    10591354
  • 负责人:
  • 金额:
    $ 209.43万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-20 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

Project Summary There is growing consensus that environmental factors influence risk for Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD). Consistent with this hypothesis, cognitive trajectories of participants in the UC Davis Alzheimer’s Disease Research Center (UCD ADRC) Longitudinal Diversity Cohort (LDC) differ geographically. These geographical differences may arise from differential exposures to environmental contaminants. In this translational study, we will test our central hypothesis that ultrafine particulate matter (UFPM) enters the brain of exposed individuals and increases risk of cognitive decline and incident AD/ADRD. Human and animal studies have largely focused on PM2.5 (fine particulate matter with an aerodynamic diameter < 2.5 µm) in AD/ADRD risk. UFPM is a subset of PM2.5. Because of its smaller size (< 0.1 µm), inhaled UFPM can cross biological barriers to gain access to multiple organs, including the brain. Our prior work found UFPM in the brain of rats exposed to traffic-related air pollution (TRAP), but not filtered air controls, indicating UFPM may be a mechanism of brain injury. To date, no human studies and few animal studies have focused specifically on UFPM in AD/ADRD. Unlike most air pollutants that are relatively spatially homogeneous, UFPM are more concentrated near pollutant sources, so they are geographically discrete. To test our hypothesis, we will leverage resources unique to UCD: (1) the LDC, which has already geocoded 500 individuals in Northern California at the census tract level with associated longitudinal cognitive measures; (2) neuropathological samples on some of these individuals, (3) an UFPM exposure model that quantifies levels and sources of specific air pollutants over the LDC capture area from 2000 to 2019; (4) brains containing UFPM from rats exposed to unchanged ambient TRAP in real time; and (5) hyperspectral and Raman spectroscopy for characterizing the chemical composition of UFPM in rat and human brains to assess brain distribution and further inform source. Using these resources, we will address the following Aims: 1. Identify the source of UFPM in brains of TgF344-AD rats exposed to TRAP and assess the spatial relationship of UFPM to AD-relevant neuropathology in rat brains. 2. Determine whether human exposure to UFPM is associated with (a) incident cognitive impairment and AD/ADRD and (b) accelerated rate of cognitive decline. 3. Initiate exploratory studies in human AD/ADRD brain samples to determine whether UFPM in select brain regions of LDC individuals are related to AD pathology. Data from this project will identify AD/ADRD-relevant neuropathology associated with UFPM, a first step in developing mechanistic hypotheses that can be tested in future studies. Additionally, this project addresses (1) biological plausibility and clinical relevance of UFPM in air pollution as an environmental factor that modifies AD/ADRD initiation and progression and contributes to AD/ADRD racial/ethnic disparities; (2) relevance of the AD/ADRD rat model to humans exposed to UFPM in polluted air; and (3) generation of data needed to support public health and regulatory strategies for controlling key sources of UFPM associated with AD/ADRD.
项目总结

项目成果

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Charles DeCarli其他文献

Charles DeCarli的其他文献

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{{ truncateString('Charles DeCarli', 18)}}的其他基金

Study of Latinos-Investigation of Neurocognitive Aging-Alzheimer's disease
拉丁裔研究-神经认知衰老-阿尔茨海默病的调查
  • 批准号:
    10629449
  • 财政年份:
    2022
  • 资助金额:
    $ 209.43万
  • 项目类别:
Study of Latinos-Investigation of Neurocognitive Aging-Alzheimer's disease
拉丁裔研究-神经认知衰老-阿尔茨海默病的调查
  • 批准号:
    10370841
  • 财政年份:
    2022
  • 资助金额:
    $ 209.43万
  • 项目类别:
Early and life course socioeconomic adversity and dementia risk in Hispanics/Latinos
西班牙裔/拉丁裔的早期和生命历程社会经济逆境和痴呆风险
  • 批准号:
    10445900
  • 财政年份:
    2022
  • 资助金额:
    $ 209.43万
  • 项目类别:
Early and life course socioeconomic adversity and dementia risk in Hispanic/Latinos
西班牙裔/拉丁裔的早期和生命历程社会经济逆境和痴呆风险
  • 批准号:
    10831329
  • 财政年份:
    2022
  • 资助金额:
    $ 209.43万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10461121
  • 财政年份:
    2021
  • 资助金额:
    $ 209.43万
  • 项目类别:
UC Davis Alzheimer's Disease Research Center
加州大学戴维斯分校阿尔茨海默病研究中心
  • 批准号:
    10461120
  • 财政年份:
    2021
  • 资助金额:
    $ 209.43万
  • 项目类别:
UC Davis Alzheimer's Disease Research Center
加州大学戴维斯分校阿尔茨海默病研究中心
  • 批准号:
    10666428
  • 财政年份:
    2021
  • 资助金额:
    $ 209.43万
  • 项目类别:
Neuroimaging Core
神经影像核心
  • 批准号:
    10461128
  • 财政年份:
    2021
  • 资助金额:
    $ 209.43万
  • 项目类别:
Neuroimaging Core
神经影像核心
  • 批准号:
    10666453
  • 财政年份:
    2021
  • 资助金额:
    $ 209.43万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10666429
  • 财政年份:
    2021
  • 资助金额:
    $ 209.43万
  • 项目类别:

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