P030 - HOUSE DUST MITE-INDUCED ASTHMA EXACERBATES THE PROGRESSION OF ALZHEIMER'S DISEASE (ID 1673)
Abstract
Aims
Alzheimer's disease (AD) is an age-related neurodegenerative disorder affecting around 35 million individuals worldwide. Besides aging, various comorbid factors increase the risk of AD, including air pollution and asthma. Epidemiological studies have reported a 2.17-fold higher risk of dementia in asthmatic patients. However, the molecular mechanism(s) underlying this asthma-associated AD exacerbation is not known. This study was designed to explore house dust mite-induced asthma effects on AD-related brain changes using the AppNL-G-F transgenic mouse model.
Methods
Male and female C57BL/6 wild type and AppNL-G-F mice (8-9 months old) were exposed to either saline or house dust mite (dose: 833μg/kg in saline) every alternate day for 16 weeks. Mice were sacrificed at the end of the experiment, and broncho-alveolar lavage fluid (BALF), lungs, and brains were collected. BALF was analyzed for immune cell markers and inflammatory mediators. In addition, Alcian blue and Masson's trichrome staining was performed on lung sections while brain sections were immunostained for Aβ. Finally, frozen hippocampi were used to perform Aβ ELISAs.
Results
As expected, the asthma-induced group showed increased pulmonary inflammatory cells, cytokine levels, and mucus and collagen production. Interestingly, hippocampi from asthma-induced mice had elevated Aβ plaque load and increased levels of soluble Aβ 1-40/42 and insoluble Aβ 1-40.
Conclusions
Based on our study, increasing cases of both diseases, and their comorbidity with age, understanding a mechanistic relationship tying progression of AD and asthma may provide a novel therapeutic intervention for both chronic diseases.
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