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Besides overt injuries, concerns also exist over the potential adverse consequences of subclinical blast exposures, which are common for many service members. A TBI is a risk factor for the later development of neurodegenerative diseases, including Alzheimer disease (AD)-like disorders. Studies of acute TBI in humans and animals have suggested that increased processing of the amyloid precursor protein (APP) toward the amyloid beta protein (A\u03b2) may explain the epidemiological associations with AD. In a previous study, however, we found in both rat and mouse models of blast overpressure exposure that rather than increasing, rodent brain A\u03b242 levels were decreased after acute blast exposure. Here we subjected APP\/presenilin 1 transgenic mice (APP\/PS1 Tg) to an extended sequence of repetitive low-level blast exposures (34.5\u2009kPa) administered three times per week over eight weeks. If initiated at 20 weeks of age, these repetitive exposures, which were designed to mimic human subclinical blast exposures, reduced anxiety and improved cognition as well as social interactions in APP\/PS1 Tg mice, returning many behavioral parameters in APP\/PS1 Tg mice to levels of non-transgenic wild type mice. Repetitive low-level blast exposure was less effective at improving behavioral deficits in APP\/PS1 Tg mice when begun at 36 weeks of age. While amyloid plaque loads were unchanged, A\u03b2 42 levels and A\u03b2 oligomers were reduced in the brain of mice exposed to repetitive low-level blast exposures initiated at 20 weeks of age, although levels did not directly correlate with behavioral parameters in individual animals. These results have implications for understanding the nature of blast effects on the brain and their relationship to human neurodegenerative diseases.<\/jats:p>","DOI":"10.1089\/neu.2021.0184","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T04:42:57Z","timestamp":1628224977000},"page":"3146-3173","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Repetitive Low-Level Blast Exposure Improves Behavioral Deficits and Chronically Lowers A\u03b242 in an Alzheimer Disease Transgenic Mouse Model"],"prefix":"10.1177","volume":"38","author":[{"given":"Georgina","family":"Perez Garcia","sequence":"first","affiliation":[{"name":"Research and Development Service, James J. 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