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The efficacy of EA was assessed by the Morris water maze\u00a0cognitive functional tests. Brain magnetic resonance imaging\u2013positron emission tomography (PET) scans using [<jats:sup>18<\/jats:sup>F]TZ4877 targeting sphingosine\u20101\u2010phosphate receptor 1 (S1PR1) and [<jats:sup>18<\/jats:sup>F]AV45 targeting amyloid beta fibrils were conducted. The correlation between regional\u00a0brain PET quantifications\u00a0and cognitive functions was analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>EA significantly\u00a0improved cognitive and memory\u00a0functions of AD (<jats:italic>p<\/jats:italic>\u00a0 = 0.04) and reduced the uptake of [<jats:sup>18<\/jats:sup>F]TZ4877 in the cortex (<jats:italic>p<\/jats:italic>\u00a0 = 0.02) and hippocampus (<jats:italic>p<\/jats:italic>\u00a0 = 0.03). Immunofluorescence confirmed colocalizations of S1PR1 with glial fibrillary acidic protein and ionized calcium\u2010binding adaptor molecule\u20101. Furthermore, immunohistochemistry showed a significant reduction of interleukin 1\u03b2 and tumor necrosis factor \u03b1 after EA treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>EA may reverse AD by suppressing neuroinflammation, and the PET imaging of S1PR1 seemed potent in evaluating the treatment for AD patients<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Electro\u2010acupuncture (EA) was administered to APP\/PS1 Alzheimer's disease (AD) mice, with untreated AD, and wild type (WT) mice serving as controls. The efficacy of EA was assessed by the Morris water maze cognitive functional tests and positron emission tomography (PET) imaging quantifications.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>PET tracer [<jats:sup>18<\/jats:sup>F]AV45 was used to detect amyloid beta deposition. An increased uptake of [<jats:sup>18<\/jats:sup>F]AV45 was found in AD compared to WT mice, with significance observed only in the cortex and not in the hippocampus. EA treatment exhibited a trend toward reduced [<jats:sup>18<\/jats:sup>F]AV45 uptake in AD mouse brains post\u2010treatment. However, statistical difference was not attained in most brain regions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>EA \u201cBaihui (DU20) and Sishencong (EX\u2010HN1)\u201d significantly improved cognitive and memory functions of AD (<jats:italic>p<\/jats:italic> = 0.04). Brain magnetic resonance imaging p(MRI)\u2013positron emission tomography (PET) quantifications revealed that significantly reduced the uptake of [<jats:sup>18<\/jats:sup>F]TZ4877 in the cortex (<jats:italic>p<\/jats:italic> = 0.02) and hippocampus (<jats:italic>p<\/jats:italic> = 0.03) after EA treatment.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The correlation between PET quantifications and cognitive functions was analyzed and the most notable correlations were found between escape latency (reaction cognitive and memory behavior) and volume distribution (V<jats:sub>T<\/jats:sub>) quantifications of [<jats:sup>18<\/jats:sup>F]TZ4877. V<jats:sub>T<\/jats:sub> quantifications of [<jats:sup>18<\/jats:sup>F]TZ4877 in key brain regions for cognitive and memory ability, such as the cortex and hippocampus, positively correlated with platform latency (cortex <jats:italic>p<\/jats:italic> &lt; 0.01, <jats:italic>r<\/jats:italic> = 0.7102; hippocampus <jats:italic>p<\/jats:italic> &lt; 0.01, <jats:italic>r<\/jats:italic> = 0.6891).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Immunofluorescence confirmed colocalizations of S1PR1 with glial fibrillary acidic protein and ionized calcium\u2010binding adaptor molecule\u20101 in the AD brain. And the EA treatment significantly reduced the signals in the cortex and hippocampus.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Immunohistochemistry showed a significant reduction of interleukin 1\u03b2 and tumor necrosis factor \u03b1 after EA treatment. EA reversed AD by suppressing neuroinflammation in the cortex and hippocampus.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The S1PR1 targeting PET tracer [<jats:sup>18<\/jats:sup>F]TZ4877 showed promise in evaluating the pathological progression of AD in clinical settings.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14260","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T12:27:14Z","timestamp":1727267234000},"page":"8331-8345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Effectiveness of electro\u2010acupuncture for cognitive improvement on Alzheimer's disease quantified via PET imaging of sphingosine\u20101\u2010phosphate receptor 1"],"prefix":"10.1002","volume":"20","author":[{"given":"Lu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chinese Medicine Oncology Cancer Center The Fifth Affiliated 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