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AD is not driven by a single factor but by the interaction of multiple pathological processes, including amyloid\u2010\u03b2 (A\u03b2) accumulation, tau hyperphosphorylation, and chronic neuroinflammation. A\u03b2 aggregates into plaques that disrupt neuronal signaling, while hyperphosphorylated tau forms neurofibrillary tangles, leading to neuronal loss. These processes act synergistically to amplify toxicity. Persistent activation of microglia and astrocytes further promotes neuroinflammation, worsening A\u03b2 and tau pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Current Limitations<\/jats:title>\n                    <jats:p>Single\u2010target therapies directed at A\u03b2 or tau have shown limited clinical success and failed to alter disease progression, underscoring the complexity of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In response, multi\u2010target\u2010directed ligands (MTDLs) have emerged as a promising strategy. By simultaneously modulating several disease pathways, MTDLs can inhibit A\u03b2 aggregation, reduce tau phosphorylation, and exert antioxidant and anti\u2010inflammatory effects. This review summarizes recent progress on MTDLs, highlighting their mechanisms of action, representative drug candidates, and outcomes from preclinical and clinical studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Multi\u2010target strategies have the potential to achieve more effective and disease\u2010modifying outcomes than conventional approaches. A critical evaluation of their opportunities and challenges may guide future therapeutic development and the advancement of precision medicine for Alzheimer's disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70919","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T08:14:37Z","timestamp":1779092077000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Multi\u2010Target\u2010Directed Ligands (\n                    <scp>MTDLs<\/scp>\n                    ) as Potential Therapeutic Candidates Targeting Multiple Pathogenic Factor of Alzheimer's Disease"],"prefix":"10.1002","volume":"32","author":[{"given":"Jaewoon","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, College of Life Science and Biotechnology Dongguk University  Seoul Republic of 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