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Beta\u2010synuclein was higher in aDS and more pronounced in sDS (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.0001), whereas pTau181 was only higher in sDS (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.0001). Both markers showed good discriminatory power (area under the curve &gt;\u20090.90) to distinguish symptomatic from asymptomatic AD. The data indicate that synaptic alterations belong to the earliest AD\u2010associated events in DS and highlight the value of serum beta\u2010synuclein as a potential early marker of AD. 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