{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:31:36Z","timestamp":1785843096486,"version":"3.56.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007214","name":"VELUX Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007214","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013297","name":"Eurostars","doi-asserted-by":"publisher","award":["12748"],"award-info":[{"award-number":["12748"]}],"id":[{"id":"10.13039\/100013297","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme\u2014Fast Track to Innovation"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Dement."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alzheimer\u2019s disease (AD) is a continuum between normal health and dementia with a long preclinical phase, during which AD pathologies start to emerge, but where there are not yet any overt symptoms. The hallmark pathologies of AD are extracellular\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -amyloid (A\u03b2) plaques and intra-neuronal neurofibrillary tangles (NFTs). A\u03b2 deposition is present at the preclinical stage. Additionally, raised microglial activation is a key factor in AD. However, its exact timing and role is still unclear. This exploratory study investigated the prevalence of microglial activation and its association with A\u03b2 deposition and memory impairment in preclinical AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 19 preclinical AD subjects with no cognitive complaints but abnormal A\u03b2 deposition present on\n                      <jats:sup>11<\/jats:sup>\n                      C-Pittsburgh Compound B (\n                      <jats:sup>11<\/jats:sup>\n                      C-PiB PET) and 10 healthy subjects with no cognitive complains or abnormal A\u03b2 deposition on\n                      <jats:sup>11<\/jats:sup>\n                      C-PiB PET underwent\n                      <jats:sup>11<\/jats:sup>\n                      C-PK11195 PET (\n                      <jats:sup>11<\/jats:sup>\n                      C-PK). Additionally, the preclinical AD subjects underwent formal cognitive testing with sensitive memory tests, including the Rey Auditory Verbal Learning Test, the Rey Complex Figure Test, and the Face-Name Associative Memory Exam.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Microglial activation was raised in occipital and parietal cortices in preclinical AD subjects compared to healthy controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01). In the preclinical subjects there were significant positive correlations between A\u03b2 load and microglial activation in parietal areas (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01). Finally, in the preclinical subjects, there were significant negative correlations between microglial activation and memory test performance in selected cortical areas (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Microglial activation was significantly raised in preclinical AD cases with no cognitive complaints and associated with impaired memory test performance. This suggests that microglial activation is present before overt clinical symptoms emerge and may be detrimental to cognition even at this early stage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/frdem.2025.1745571","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T05:25:15Z","timestamp":1769491515000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Microglial activation is raised in preclinical Alzheimer\u2019s disease and associated with covert memory impairment"],"prefix":"10.3389","volume":"4","author":[{"given":"Pernille Louise","family":"Kjeldsen","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University","place":["Aarhus, Denmark"]},{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital","place":["Aarhus, Denmark"]},{"name":"Centre of Functionally Integrative Neuroscience, Aarhus University","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasse Stensvig","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University","place":["Aarhus, Denmark"]},{"name":"Centre of Functionally Integrative Neuroscience, Aarhus University","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Parbo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University","place":["Aarhus, Denmark"]},{"name":"Department of Nuclear Medicine, Odense University Hospital","place":["Odense, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rola","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Vejle Hospital","place":["Vejle, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel Fredrik Astrup","family":"Aanerud","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malene","family":"Kaasing","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University","place":["Aarhus, Denmark"]},{"name":"Centre of Functionally Integrative Neuroscience, Aarhus University","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malene Flensborg","family":"Damholdt","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University","place":["Aarhus, Denmark"]},{"name":"Department of Psychology, Aarhus University","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Fristed","family":"Eskildsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University","place":["Aarhus, Denmark"]},{"name":"Centre of Functionally Integrative Neuroscience, Aarhus University","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"\u00d8stergaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University","place":["Aarhus, Denmark"]},{"name":"Centre of Functionally Integrative Neuroscience, Aarhus University","place":["Aarhus, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David James","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University","place":["Aarhus, Denmark"]},{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital","place":["Aarhus, Denmark"]},{"name":"Translational and Clinical Research Institute, Newcastle University","place":["Newcastle upon Tyne, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref2","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1001\/archneur.65.11.1509","article-title":"Frequent amyloid deposition without significant cognitive impairment among the elderly","volume":"65","author":"Aizenstein","year":"2008","journal-title":"Arch. 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