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This review provides an integrative overview of the molecular and biochemical modulators governing synaptic plasticity and their disruption in AD. We discuss how the collective impairment of A\u03b2 aggregation, tau pathology, calcium imbalance, oxidative stress, and neuroinflammation affects dendritic spine morphology and synaptic connectivity. Particular attention is given to neurotrophins such as brain-derived neurotrophic factor and TrkB signaling, hormonal influences, likewise glucocorticoids, estrogens, testosterone, endocannabinoid pathways, lipid and cholesterol regulators like ApoE and lipid rafts, and epigenetic mechanisms that modulate synaptic resilience. We further evaluate the therapeutic potential of pharmacological agents, including cholinesterase inhibitors, NMDA receptor modulators, and multi-target directed ligands alongside nutraceuticals such as resveratrol, curcumin, omega-3 fatty acids,\n                    <jats:italic toggle=\"yes\">Withania somnifera<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">Bacopa monnieri<\/jats:italic>\n                    . Emerging technologies, including iPSC-derived neuronal models, optogenetics, and advanced neuroimaging biomarkers like SV2A PET, cerebrospinal fluid\/plasma neurogranin, are also highlighted for their role in elucidating and monitoring synaptic integrity. Ultimately, targeting the biochemical modulators of synaptic plasticity offers a promising avenue for AD therapy, especially through combinatorial and precision-medicine strategies aimed at restoring synaptic function and cognitive performance.\n                  <\/jats:p>","DOI":"10.1177\/13872877261469864","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T13:40:08Z","timestamp":1784814008000},"page":"501-518","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Biochemical modulators of synaptic plasticity: New horizons in Alzheimer's disease treatment"],"prefix":"10.1177","volume":"113","author":[{"given":"Iqra","family":"Farzeen","sequence":"first","affiliation":[{"name":"Department of Zoology, Government College University, Faisalabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad 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