Association between PM2.5 exposure by inhalation and brain damages of Alzheimer&#8217;s disease in transgenic mice
Authors: fu pengfei , Yung Ken Kin Lam 
Published: March 2020

&lt;p&gt;&lt;strong&gt;Title&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Association between PM&lt;sub&gt;2.5&lt;/sub&gt; exposure by inhalation and brain damages of Alzheimer&amp;#8217;s disease in transgenic mice &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&amp;#160;&lt;/strong&gt;Pengfei Fu &lt;sup&gt;a,b&lt;/sup&gt;,&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Corresponding author&lt;/strong&gt;&lt;strong&gt;&lt;sup&gt;&amp;#8270;&lt;/sup&gt;&lt;/strong&gt;&lt;strong&gt;: &lt;/strong&gt;Ken Kin Lam Yung &lt;sup&gt;a,b, &amp;#8270;&lt;/sup&gt; (kklyung@hkbu.edu.hk)&lt;/p&gt;&lt;p&gt;a Department of Biology, Hong Kong Baptist University, Hong Kong SAR, China.&lt;/p&gt;&lt;p&gt;b Golden Meditech Center for NeuroRegeneration Sciences&lt;/p&gt;&lt;p&gt;&amp;#160;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;ABSTRACT&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background&lt;/strong&gt;: Fine particulate matter (PM&lt;sub&gt;2.5&lt;/sub&gt;) exposure increases the risk of neurological disorders. However, the relevance between PM&lt;sub&gt;2.5&lt;/sub&gt; and Alzheimer&amp;#8217;s disease (AD) needs to be identified and the effect of PM&lt;sub&gt;2.5&lt;/sub&gt; exposure on the brain in AD mice remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective:&lt;/strong&gt; To assess the effects of PM&lt;sub&gt;2.5 &lt;/sub&gt;exposure on AD and investigate the brain damage in AD transgenic mice exposed to PM&lt;sub&gt;2.5&lt;/sub&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; We searched articles from the database of PubMed for meta-analyses on the association between PM&lt;sub&gt;2.5&lt;/sub&gt; exposure and AD. Further, using a novel real-world whole-body inhalation exposure system, wild type (WT) and APP/PS1 transgenic mice (AD mice) were respectively exposed to filtered air (FA) or ambient PM&lt;sub&gt;2.5&lt;/sub&gt; for 8 weeks in Taiyuan, China. The pathological and ultrastructural changes and levels of A&amp;#946;-42, TNF-&amp;#945;, and IL-6 in brains in FA-WT mice, FA-AD mice, FA-PM&lt;sub&gt;2.5&lt;/sub&gt; mice, and PM&lt;sub&gt;2.5&lt;/sub&gt;-AD mice were measured.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; Long-term PM&lt;sub&gt;2.5&lt;/sub&gt; exposure had the association with increased risks of dementia and AD by OR of 1.16 (95% CI 1.07&amp;#8211;1.26) and 3.26 (95% CI 0.84&amp;#8211;12.74) via meta-analysis. Both lightly- and heavily polluted countries showed such increased risks. In the open field test, the PM&lt;sub&gt;2.5&lt;/sub&gt;-AD mice showed more significant degenerative symptoms of AD by the behavioral change in movement. Hematoxylin-eosin staining results showed that noticeable histopathological injury such as structural disorder, hyperemia, and sporadic inflammatory cell infiltration in the brain of PM&lt;sub&gt;2.5&lt;/sub&gt;-AD mice, and transmission electron microscope results displayed that serious damage in the brain in PM&lt;sub&gt;2.5&lt;/sub&gt;-AD mice, which maintained disorder of cristae and vacuolation of mitochondria, synaptic abnormalities, and loose myelin sheaths. A&amp;#946;-42, TNF-&amp;#945; and IL-6 levels in brains of PM&lt;sub&gt;2.5&lt;/sub&gt;-AD mice had raised more strongly than that of FA-WT or FA-AD mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study indicated a strong association between PM&lt;sub&gt;2.5&lt;/sub&gt; exposure and AD risks. PM&lt;sub&gt;2.5&lt;/sub&gt; significantly aggravated the severity of neuronal pathomorphological changes and inflammation in AD mice when A&amp;#946;-42 levels in the brain were visibly increased.&lt;/p&gt;&lt;p&gt;&amp;#160;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Acknowledgment:&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;Car-SCs Treatment Technology and Study the Application of Inorganic Nanomatrices on MSC T-cells Proliferation (Project Ref: RMGS-2019-1-03).&lt;/p&gt;