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While some studies suggest that neuroinflammation potentiates neurodegeneration, others indicate a protective effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We evaluated 145 individuals with positron emission tomography (PET) for amyloid beta (A\u03b2), tau, and translocator protein (TSPO), a proxy of neuroinflammation, to test the hypothesis that A\u03b2 and tau are associated with the dual effect of neuroinflammation on neurodegeneration across the AD continuum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The detrimental effects of neuroinflammation on gray matter density occurred in two waves. The first neuroinflammation\u2010related detrimental wave was associated with brain A\u03b2 deposition, while the second was with widespread tau tangle pathology. Furthermore, the concomitant presence of neuroinflammation, A\u03b2, and tau was associated with faster cognitive decline over 2 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Our results support a model in which A\u03b2\u2010 and tau\u2010associated neuroinflammation are related to two waves of deleterious effects on AD\u2010related neurodegeneration.<\/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>Two waves of detrimental neuroinflammation effects on brain density associated with A\u03b2 or tau.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>A\u03b2 associated with deleterious effect of neuroinflammation on brain density in early AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tau associated with deleterious effect of neuroinflammation on brain density in late AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Interactions of A\u03b2, tau, and neuroinflammation are associated with cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70746","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:17:17Z","timestamp":1759144637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Amyloid beta and tau are associated with the dual effect of neuroinflammation on neurodegeneration"],"prefix":"10.1002","volume":"21","author":[{"given":"Guilherme","family":"Povala","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Bellaver","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Ant\u00f4nio De","family":"Bastiani","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Biochemistry Universidade Federal do Rio Grande do Sul  Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro","family":"Ferrari\u2010Souza","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Biochemistry Universidade Federal do Rio Grande do Sul  Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiano S.","family":"Aguzzoli","sequence":"additional","affiliation":[{"name":"Brain Institute of Rio Grande do Sul PUCRS  Porto Alegre Rio Grande do Sul Brazil"},{"name":"Global Brain Health Institute University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas T.","family":"Leffa","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela C. 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