{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T15:23:59Z","timestamp":1789572239635,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Chronic air pollution (AirPoll) is associated with accelerated cognitive decline and risk of Alzheimer's disease (AD). Correspondingly, wild\u2010type and AD\u2010transgenic rodents exposed to AirPoll have increased amyloid peptides and behavioral impairments.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We examined the \u03b3\u2010secretase modulator GSM\u201015606 for potential AirPoll protection by its attenuating of amyloid beta (A\u03b2)42 peptide production. Male and female wild\u2010type mice were fed GSM\u201015606 during an 8\u2010week inhalation exposure to AirPoll subfractions, ambient nanoparticulate matter (nPM), and diesel exhaust particles (DEP).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>GSM\u201015606 decreased A\u03b242 during nPM and DEP exposure without changing beta\u2010 or gamma\u2010secretase activity or BACE1 and PS1 protein levels. DEP increased lateral ventricle volume by 25%.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>These enzyme responses are relevant to AD drug treatments, as well as to the physiological functions of the A\u03b242 peptide. GSM\u201015606 attenuation of A\u03b242 may benefit human exposure to AirPoll.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Gamma\u2010secretase modulator (GSM\u201015606) attenuates the amyloidogenic amyloid beta (A\u03b2)42 peptide during exposure to air pollution, which may be a mechanism by which air pollution increases Alzheimer's disease (AD) risk.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>AD drug treatments may also consider A\u03b2 homeostasis among the chronic effects of GSM\u201015606 and other amyloid reduction treatments on secretase enzymes.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14086","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T07:00:17Z","timestamp":1723446017000},"page":"6107-6114","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Air pollution amyloidogenesis is attenuated by the gamma\u2010secretase modulator GSM\u201015606"],"prefix":"10.1002","volume":"20","author":[{"given":"Jose A.","family":"Godoy\u2010Lugo","sequence":"first","affiliation":[{"name":"Leonard Davis School of Gerontology University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max A.","family":"Thorwald","sequence":"additional","affiliation":[{"name":"Leonard Davis School of Gerontology University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mafalda","family":"Cacciottolo","sequence":"additional","affiliation":[{"name":"Leonard Davis School of Gerontology University of Southern California  Los Angeles California USA"},{"name":"Capricor Therapeutics, Inc.  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