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Some studies reported higher Hg levels in AD patients, but evidence is inconclusive. Mechanisms linking Hg exposure to AD neuropathology remain to be found. The hallmark of AD brains is deposits of insoluble amyloid plaques consisting mainly of aggregated amyloid\u2010\u03b2 (A\u03b2) peptides. Here, we use transmission electron microscopy and biophysical spectroscopy techniques to study in vitro interactions between inorganic Hg and pathologically relevant A\u03b2(1\u201340) and A\u03b2(4\u201340) variants and the A\u03b2(1\u201340)(H6A, H13A, H14A) mutant. For the first time, effects on A\u03b2 aggregation of both Hg(I) and Hg(II) are compared. Hg(II) binds A\u03b2(1\u201340) with apparent binding affinity of 28\u2009\u00b1\u20098\u2009\u03bcM, at 20\u2009\u00b0C in 20\u2009mM MES buffer, pH 7.3. The N\u2010terminal His6, His13, and His14 residues are involved in binding coordination. Hg(II) binding induces structural alterations (coil\u2013coil interactions) in A\u03b2 monomers positioned in membrane\u2010mimicking SDS micelles. Equimolar amounts of either Hg(I) or Hg(II) inhibit normal A\u03b2 fibrillation by directing aggregation towards forming large amorphous aggregates. All these structural rearrangements may be relevant for the harmful A\u03b2 aggregation processes involved in AD brain pathology. Inducing protein misfolding and aggregation might be a general toxic mechanism of mercury.<\/jats:p>","DOI":"10.1002\/cbic.202500252","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T20:03:16Z","timestamp":1746043396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Binding of Hg(I) and Hg(II) Ions to Amyloid\u2010Beta (A\u03b2) Peptide Variants Affect their Structure and Aggregation"],"prefix":"10.1002","volume":"26","author":[{"given":"Elina","family":"Berntsson","sequence":"first","affiliation":[{"name":"Chemistry Section Stockholm University  10691 Stockholm Sweden"},{"name":"Department of Chemistry and Biotechnology Tallinn University of Technology  12618 Tallinn Estonia"},{"name":"CellPept Sweden AB  Kvarngatan 10B 11847 Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andra","family":"Noorm\u00e4gi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology Tallinn University of Technology  12618 Tallinn Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e4rt","family":"Padari","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology University of Tartu  50411 Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcri","family":"Jarvet","sequence":"additional","affiliation":[{"name":"Chemistry Section Stockholm University  10691 Stockholm Sweden"},{"name":"CellPept Sweden AB  Kvarngatan 10B 11847 Stockholm Sweden"},{"name":"The National Institute of Chemical Physics and Biophysics  12618 Tallinn Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Gr\u00e4slund","sequence":"additional","affiliation":[{"name":"CellPept Sweden AB  Kvarngatan 10B 11847 Stockholm Sweden"},{"name":"Department of Biophysics and Biochemistry Stockholm University  10691 Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margus","family":"Pooga","sequence":"additional","affiliation":[{"name":"CellPept Sweden AB  Kvarngatan 10B 11847 Stockholm Sweden"},{"name":"Institute of Technology University of Tartu  50411 Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peep","family":"Palumaa","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology Tallinn University of Technology  12618 Tallinn Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-1838","authenticated-orcid":false,"given":"Sebastian K. 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