{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:23:24Z","timestamp":1792041804562,"version":"4.4.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The recent introduction of immunotherapeutic agents targeting amyloid-\u03b2 (A\u03b2) has advanced the pharmacological treatment of Alzheimer\u2019s disease (AD). Although several anti-A\u03b2 antibodies have dramatically reduced cerebral amyloid plaques, this has not translated into major cognitive or clinical benefits, thus questioning the clinical relevance of these biomarker changes. Indeed, there is an ongoing debate over whether amyloid reduction alone constitutes sufficient evidence of disease modification to justify regulatory approval.<\/jats:p>\n                  <jats:p>Against this backdrop, we propose a third pathway that transcends the binary framework of molecular versus clinical end points by positioning brain connectivity as a system-level intermediate phenotype. This approach is supported by a growing body of evidence. Alterations in brain networks are early, sensitive, and modifiable markers of AD pathology. Connectivity metrics capture the dynamic interplay between genetic and environmental factors, offering a unified model of disease. Advances in precision medicine, such as individualized connectivity \u2018fingerprints\u2019 and the emergence of digital twins, further position brain connectivity as a powerful platform for therapeutic innovation.<\/jats:p>\n                  <jats:p>We argue that adopting brain network analysis as a key outcome measure enables a shift beyond isolated biomarker achievements toward a more integrated, biologically grounded, and clinically meaningful framework for disease modification in AD, bridging the gap between molecular advances and real-world impact.<\/jats:p>","DOI":"10.1093\/brain\/awaf404","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T11:32:25Z","timestamp":1761046345000},"page":"432-438","source":"Crossref","is-referenced-by-count":11,"title":["Brain connectivity as a new target for Alzheimer\u2019s disease therapy?"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9305-3376","authenticated-orcid":false,"given":"Lorenzo","family":"Pini","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Padova , Padova 35123 \u00a0","place":["Italy"]},{"name":"Padova Neuroscience Center, University of Padova , Padova 35123 \u00a0","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4455-6719","authenticated-orcid":false,"given":"Gilles","family":"Allali","sequence":"additional","affiliation":[{"name":"Leenaards Memory Center, Lausanne University Hospital and University of Lausanne , Lausanne 1011 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0327-7262","authenticated-orcid":false,"given":"Bruno P","family":"Imbimbo","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Chiesi Farmaceutici , Parma 43122 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Germani","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Chiesi Farmaceutici , Parma 43122 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Corbetta","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Padova , Padova 35123 \u00a0","place":["Italy"]},{"name":"Padova Neuroscience Center, University of Padova , Padova 35123 \u00a0","place":["Italy"]},{"name":"Veneto Institute of Molecular Medicine (VIMM) , Padova 35123 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