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Indeed, after more than 40 AD trials of anti-amyloid interventions, reduction of amyloid-\u03b2 (A\u03b2) has never translated into clinically relevant benefits, and in several cases yielded harm. The fundamental problem is the century-old, brain-centric phenotype-based definitions of diseases that ignore causal mechanisms and comorbidities. In this hypothesis article, we discuss how such current outdated nosology of dementia is a key roadblock to precision medicine and articulate how Network Medicine enables the substitution of clinicopathologic phenotypes with molecular endotypes and propose a new framework to achieve precision and curative medicine for patients with neurodegenerative disorders.<\/jats:p>","DOI":"10.3233\/jad-230694","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T11:42:35Z","timestamp":1695382955000},"page":"47-56","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Re-Addressing Dementia by Network Medicine and Mechanism-Based Molecular Endotypes"],"prefix":"10.1177","volume":"96","author":[{"given":"Mayra","family":"Pacheco Pachado","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Personalised Medicine, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana I.","family":"Casas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Personalised Medicine, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands"},{"name":"Universit\u00e4tsklinikum Essen, Klinik f\u00fcr Neurologie, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud H.","family":"Elbatreek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Personalised Medicine, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Nogales","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Personalised Medicine, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emre","family":"Guney","sequence":"additional","affiliation":[{"name":"Discovery and Data Science (DDS) Unit, STALICLA R&D SL, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto J.","family":"Espay","sequence":"additional","affiliation":[{"name":"James J. and Joan A. 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