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Despite extensive research, effective therapy for AD remains elusive. Polyoxometalates (POMs), a class of inorganic compounds with diverse chemical structures and properties, are emerging as potential candidates for AD treatment due to their ability to target key molecular players implicated in disease pathogenesis, such as A\u03b2, acetylcholinesterase (AChE) and butyryl acetylcholinesterase (BChE). Here, we use molecular docking to predict the binding pose and affinities of POMs to 10 top targets associated with AD. First, we validate our method by replicating experimentally known binding of POMs to A\u03b2 (\u0394<jats:italic>G<\/jats:italic>\u2009=\u2009\u2013 9.67 kcal\/mol), AChE (\u0394<jats:italic>G<\/jats:italic>\u2009=\u2009\u2013 9.39 kcal\/mol) and BChE (\u0394<jats:italic>G<\/jats:italic>\u2009=\u2009\u2013 10.86 kcal\/mol). Then, using this method, we show that POM can also bind \u03b2-secretase 1 (BACE1, \u0394<jats:italic>G<\/jats:italic>\u2009=\u2009\u2013 10.14 kcal\/mol), presenilin 1 (PSEN1, \u0394<jats:italic>G<\/jats:italic>\u2009=\u2009\u2013 10.65 kcal\/mol), presenilin 2 (PSEN2, \u0394<jats:italic>G<\/jats:italic>\u2009=\u2009\u2013 7.94 kcal\/mol), Amyloid Precursor Protein (APP, \u0394<jats:italic>G<\/jats:italic>\u2009=\u2009\u2013 7.26 kcal\/mol), Apolipoprotein E (APOE4, \u0394<jats:italic>G<\/jats:italic>\u2009=\u2009\u2013 10.05 kcal\/mol), Microtubule-Associated Protein Tau (MAPT, \u0394<jats:italic>G<\/jats:italic>\u2009=\u2009\u2013 5.28 kcal\/mol) depending on phosphorylation, and \u03b1-synuclein (SNCA, \u0394<jats:italic>G<\/jats:italic>\u2009=\u2009\u2013 7.64 kcal\/mol). Through such binding, POMs offer the potential to mitigate APP cleavage, A\u03b2 oligomer neurotoxicity, A\u03b2 aggregation, thereby attenuating disease progression. Overall, our molecular docking study represents a powerful tool in the discovery of POM-based therapeutics for AD, facilitating the development of novel treatments for AD.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s00775-025-02111-2","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T05:23:08Z","timestamp":1742707388000},"page":"299-309","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Polyoxometalates bind multiple targets involved in Alzheimer\u2019s disease"],"prefix":"10.1007","volume":"30","author":[{"given":"Karin","family":"Ben Zaken","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rivka","family":"Bouhnik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naama","family":"Omer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naamah","family":"Bloch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham O.","family":"Samson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,22]]},"reference":[{"key":"2111_CR1","volume-title":"A new perspective on Alzheimer\u2019s disease as a brain expression of a complex metabolic disorder. 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