{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:17:42Z","timestamp":1791919062889,"version":"4.3.4"},"reference-count":63,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Beta\u2010amyloid plaques and hyperphosphorylated tau tangles are the neuropathological hallmarks of Alzheimer's disease; however, their relevance in the pathophysiology is not fully understood. It has been suggested that these larger and insoluble aggregates may not be the most toxic forms of beta\u2010amyloid and tau in Alzheimer's disease, and the disease progression may actually be promoted by the small\u2010diffusible aggregates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS AND RESULTS<\/jats:title>\n                    <jats:p>We combine the recent findings from our group and other key research to put forward the hypotheses that the formation of the small\u2010diffusible aggregates of beta\u2010amyloid and tau and their larger insoluble counterparts is not a linear process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>While the small\u2010diffusible aggregate formation of beta\u2010amyloid and tau is a passive process, regulated by thermodynamic equilibria, the formation of large\u2010insoluble aggregates is an active process, regulated by microglia and neurons, which to an extent is a protective mechanism against the toxicity of the smaller aggregates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Plaques and tangles may be made by active processes in Alzheimer's disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The small\u2010soluble aggregates may be the more toxic species in Alzheimer's disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pathology may be caused by the imbalance of production and clearance of aggregates.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plaques and tangle formation may be attempts to restore the homeostatic equilibrium.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70462","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T23:45:37Z","timestamp":1751586337000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Small\u2010diffusible aggregates, plaques, tangles, and dynamic equilibria: Untangling Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0060-5806","authenticated-orcid":false,"given":"Emre","family":"Fertan","sequence":"first","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  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