{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:03:41Z","timestamp":1788498221698,"version":"build-2803163510"},"reference-count":79,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2022,2,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Neuritic plaques contain neural and microglial elements, and amyloid-\u03b2 protein (A\u03b2), but their pathogenesis remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Elucidate neuritic plaque pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Histochemical visualization of hyperphosphorylated-tau positive (p-tau+) structures, microglia, A\u03b2, and iron.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Disintegration of large projection neurons in human hippocampus and neocortex presents as droplet degeneration: pretangle neurons break up into spheres of numerous p-tau+ droplets of various sizes, which marks the beginning of neuritic plaques. These droplet spheres develop in the absence of colocalized A\u03b2 deposits but once formed become encased in diffuse A\u03b2 with great specificity. In contrast, neurofibrillary tangles often do not colocalize with A\u03b2. Double-labelling for p-tau and microglia showed a lack of microglial activation or phagocytosis of p-tau+ degeneration droplets but revealed massive upregulation of ferritin in microglia suggesting presence of high levels of free iron. Perl\u2019s Prussian blue produced positive staining of microglia, droplet spheres, and A\u03b2 plaque cores supporting the suggestion that droplet degeneration of pretangle neurons in the hippocampus and cortex represents ferroptosis, which is accompanied by the release of neuronal iron extracellularly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Age-related iron accumulation and ferroptosis in the CNS likely trigger at least two endogenous mechanisms of neuroprotective iron sequestration and chelation, microglial ferritin expression and A\u03b2 deposition, respectively, both contributing to the formation of neuritic plaques. Since neurofibrillary tangles and A\u03b2 deposits colocalize infrequently, tangle formation likely does not involve release of neuronal iron extracellularly. In human brain, targeted deposition of A\u03b2 occurs specifically in response to ongoing ferroptotic droplet degeneration thereby producing neuritic plaques.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-215334","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T10:30:27Z","timestamp":1640341827000},"page":"1701-1720","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":32,"title":["Droplet Degeneration of Hippocampal and Cortical Neurons Signifies the Beginning of Neuritic Plaque Formation"],"prefix":"10.1177","volume":"85","author":[{"given":"Wolfgang J.","family":"Streit","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Rotter","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, 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