{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:53:43Z","timestamp":1779886423052,"version":"3.53.1"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>\n                    We undertook longitudinal \u03b2-amyloid positron emission tomography (A\u03b2-PET) imaging as a translational tool for monitoring of chronic treatment with the peroxisome proliferator-activated receptor gamma (PPAR\u03b3) agonist pioglitazone in A\u03b2 model mice. We thus tested the hypothesis this treatment would rescue from increases of the A\u03b2-PET signal while promoting spatial learning and preservation of synaptic density. Here, we investigated longitudinally for 5 months PS2APP mice (\n                    <jats:italic>N<\/jats:italic>\n                    = 23; baseline age: 8 months) and\n                    <jats:italic>\n                      App\n                      <jats:sup>\n                        <jats:italic>NL<\/jats:italic>\n                        \u2013\n                        <jats:italic>G<\/jats:italic>\n                        \u2013\n                        <jats:italic>F<\/jats:italic>\n                      <\/jats:sup>\n                    <\/jats:italic>\n                    mice (\n                    <jats:italic>N<\/jats:italic>\n                    = 37; baseline age: 5 months) using A\u03b2-PET. Groups of mice were treated with pioglitazone or vehicle during the follow-up interval. We tested spatial memory performance and confirmed terminal PET findings by immunohistochemical and biochemistry analyses. Surprisingly, A\u03b2-PET and immunohistochemistry revealed a shift toward higher fibrillary composition of A\u03b2-plaques during upon chronic pioglitazone treatment. Nonetheless, synaptic density and spatial learning were improved in transgenic mice with pioglitazone treatment, in association with the increased plaque fibrillarity. These translational data suggest that a shift toward higher plaque fibrillarity protects cognitive function and brain integrity. Increases in the A\u03b2-PET signal upon immunomodulatory treatments targeting A\u03b2 aggregation can thus be protective.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2022.854031","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T14:51:25Z","timestamp":1648651885000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Chronic PPAR\u03b3 Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition"],"prefix":"10.3389","volume":"14","author":[{"given":"Tanja","family":"Blume","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Deussing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Biechele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Zott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Franzmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Wind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Eckenweber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Sacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Ochs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gernot","family":"Kleinberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianyuan","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Focke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lindner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz-Josef","family":"Gildehaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Beyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"von Ungern-Sternberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bartenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlheinz","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmuth","family":"Adelsberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Rominger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Cumming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Willem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario M.","family":"Dorostkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Herms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Brendel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1101\/2021.05.30.446348","article-title":"Chronic PPAR\u03b3 Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition.","author":"Biechele","year":"2021","journal-title":"bioRxiv"},{"key":"B2","doi-asserted-by":"publisher","first-page":"117","DOI":"10.2967\/jnumed.120.261858","article-title":"Glitter in the Darkness? 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