{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:39:27Z","timestamp":1792661967791,"version":"4.5.0"},"reference-count":0,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000049","name":"national institute on aging","doi-asserted-by":"publisher","award":["R01 AG062285, P30 AG062715, R01 AG027161"],"award-info":[{"award-number":["R01 AG062285, P30 AG062715, R01 AG027161"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"eunice kennedy shriver national institute of child health and human development","doi-asserted-by":"publisher","award":["P50 HD105353"],"award-info":[{"award-number":["P50 HD105353"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health Office of the Director","award":["S10 OD025245"],"award-info":[{"award-number":["S10 OD025245"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"abstract":"<jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>\n                      Synaptic loss is one of the strongest post-mortem predictors of Alzheimer's disease (AD) severity and may impact how pathology affects cognition. This study compared regional [\n                      <jats:sup>11<\/jats:sup>\n                      C]UCB-J synaptic density across the AD continuum and evaluated the extent to which synaptic density mediates relationships between AD biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Seventy-two participants completed PET scans, MRIs, and cognitive testing. Participants were categorized into subgroups representing typical AD progression. Regional synaptic density was compared across subgroups and pathological variables. Standard mediation and moderated mediation analyses were performed using amyloid and tau as predictors\/moderators and MoCA score as outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The amyloid+\/tau+\/impaired subgroup showed lower synaptic density than controls, particularly for transverse temporal, inferior parietal, and hippocampal regions (Cohen's d=1.60, 1.57, 1.50). Hippocampal synaptic density had the strongest associations with tau (\u03b2=\u22120.473); transverse temporal synaptic density had the strongest association with amyloid (\u03b2=\u22120.543) and age (\u03b2=\u22120.614). Eight of twelve assessed brain regions demonstrated significant indirect effects across mediation frameworks. The inferior parietal lobe showed the largest mediation for amyloid (45.3%) and tau (28.9%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion:<\/jats:title>\n                    <jats:p>These findings support the hypothesis that synaptic loss is a primary mechanism contributing to clinical AD and suggest that synaptic density imaging can provide complementary information to the existing AD framework.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0271678x261501266","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:06:00Z","timestamp":1792555560000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["EXPRESS: Synaptic density PET mediates the relationship between Alzheimer\u2019s disease pathology and cognitive performance"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1801-7233","authenticated-orcid":false,"given":"Max J","family":"McLachlan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brecca","family":"Bettcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Langhough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"DiFilippo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobey","family":"Betthauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"McVea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisette","family":"LeMerise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8966-8397","authenticated-orcid":false,"given":"Matthew","family":"Zammit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Grover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin M","family":"Jonaitis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Ennis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Asthana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling C.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara B","family":"Bendlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T","family":"Christian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,20]]},"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X261501266","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X261501266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:46:35Z","timestamp":1792658795000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X261501266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":0,"alternative-id":["10.1177\/0271678X261501266"],"URL":"https:\/\/doi.org\/10.1177\/0271678x261501266","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"article-number":"0271678X261501266"}}