| RRC ID |
88515
|
| 著者 |
Greve HJ, Dunbar AL, Lombo CG, Ahmed C, Thang M, Messenger EJ, Mumaw CL, Johnson JA, Kodavanti UP, Oblak AL, Block ML.
|
| タイトル |
The bidirectional lung brain-axis of amyloid-β pathology: ozone dysregulates the peri-plaque microenvironment.
|
| ジャーナル |
Brain
|
| Abstract |
The mechanisms underlying how urban air pollution affects Alzheimer's disease (AD) are largely unknown. Ozone (O3) is a reactive gas component of air pollution linked to increased AD risk, but is confined to the respiratory tract after inhalation, implicating the peripheral immune response to air pollution in AD neuropathology. Here, we demonstrate that O3 exposure impaired the ability of microglia, the brain's parenchymal immune cells, to associate with and form a protective barrier around Aβ plaques, leading to augmented dystrophic neurites and increased Aβ plaque load. Spatial proteomic profiling analysis of peri-plaque proteins revealed a microenvironment-specific signature of dysregulated disease-associated microglia protein expression and increased pathogenic molecule levels with O3 exposure. Unexpectedly, 5xFAD mice exhibited an augmented pulmonary cell and humoral immune response to O3, supporting that ongoing neuropathology may regulate the peripheral O3 response. Circulating HMGB1 was one factor upregulated in only 5xFAD mice, and peripheral HMGB1 was separately shown to regulate brain Trem2 mRNA expression. These findings demonstrate a bidirectional lung-brain axis regulating the central and peripheral AD immune response and highlight this interaction as a potential novel therapeutic target in AD.
|
| 巻・号 |
146(3)
|
| ページ |
991-1005
|
| 公開日 |
2023-3-1
|
| DOI |
10.1093/brain/awac113
|
| PII |
6555088
|
| PMID |
35348636
|
| PMC |
PMC10169526
|
| MeSH |
Alzheimer Disease* / pathology
Amyloid beta-Peptides / metabolism
Animals
Brain / pathology
Disease Models, Animal
HMGB1 Protein*
Lung / metabolism
Lung / pathology
Membrane Glycoproteins / metabolism
Mice
Mice, Transgenic
Microglia / metabolism
Ozone* / metabolism
Ozone* / toxicity
Plaque, Amyloid / pathology
Proteomics
Receptors, Immunologic
|
| IF |
11.337
|
| リソース情報 |
| 実験動物マウス |
RBRC06240 |
