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Does air pollution increase risk of AD in a genetically susceptible animal model?

空气污染是否会增加遗传易感动物模型患 AD 的风险？

基本信息

批准号：
9126737
负责人：
Pamela J Lein
金额：
$ 23.54万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9126737
关键词：
Address Age Age of Onset Age-Months Air Air Pollution Alzheimer&apos s Disease Alzheimer&apos s disease risk Amyloid beta-Protein Amyloid beta-Protein Precursor Animal Housing Animal Model Animals Archives Area Autonomic ganglion Behavioral Biological Markers Blood Brain Breathing Cerebral cortex Characteristics Chemicals Chronic Clinical Commuting Consensus Control Animal Data Development Diesel Exhaust Diffuse Disease Progression Dose Early Onset Familial Alzheimer&apos s Disease Engineering Environmental Risk Factor Epidemiologic Studies Exhibits Exposure to Female Future Gases Genes Genetic Genetic Predisposition to Disease Gliosis Goals Hippocampus (Brain)Housing Human Impaired cognition Inbred F344 Rats Inflammatory Response Learning Link Measures Memory Modeling Monitor Motor Vehicles Nerve Degeneration Neurodegenerative Disorders Neurologic Particle Size Particulate Matter Pathogenesis Pathology Patients Performance Phenotype Populations at Risk Predisposition Public Health Rattus Reflex action Reporting Resources San Francisco Senile Plaques Sex Characteristics Source Staging Susceptibility Gene Tauopathies Testing Time Transgenic Mice Transgenic Organisms United States Vehicle Emissions age related air filter air sampling base cerebral amyloidosis exhaust gene environment interaction inflammatory marker innovation juvenile animal male mutant neuroinflammation neuron loss neuropathology neurotoxic novel overexpression particle postnatal presenilin presenilin-1 public health relevance research study response risk variant sex tau mutation traffic-related air pollution

项目摘要

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease in the United States. More than 90% of cases are idiopathic and there is growing consensus that environmental factors interact with genes of susceptibility to influence the age of onset and progression of this disease. Recent epidemiological studies have reported a positive correlation between exposure to traffic-related air pollution and the occurrence of the hallmark clinical characteristics of AD, including increased expression of pro-inflammatory markers in the brain, diffuse amyloid plaques, neuronal cell loss, and impaired cognition. We hypothesize that traffic- related air pollution emitted from motor vehicles triggers inflammatory responses in the brain that initiate or accelerate the progression of AD. To test this, we will use a unique animal model: the TgF344 rat, which expresses human genes that confer susceptibility to AD. We will expose male and female TgF344 rats and their wildtype littermates to polluted air sampled directly from the Caldecott tunnel in the San Francisco area beginning at postnatal day 28 to up to 12 months of age. Caldecott tunnel air will be delivered to animals housed in a portable vivarium parked adjacent to the tunnel. Control animals will be exposed to clean filtered air. Caldecott tunnel air will be collected every three weeks for gas and particle chemical characterization, and both Caldecott tunnel air and clean filtered air will be monitored continuously for particle size distribution and concentration. Learning and memory as well as neuroinflammation and AD-like pathology will be assessed in animals at 3, 6, 9 and 12 months of age. These studies will provide proof-of-concept data identifying functionally relevant interactions between AD-linked genetic susceptibilities and a ubiquitous environmental risk factor.