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An effective therapy has not been implicated yet, which is in part also due to the fact that pathological changes occur years before clinical symptoms manifest. Thus, there is a great need for the development of a translatable biomarker. Recent evidence highlights microRNAs as candidate biomarkers. In this study, we use next-generation sequencing to study the small noncoding RNAome (sncRNAome) in exosomes derived from human cerebrospinal fluid (CSF). We show that the sncRNAome from CSF-derived exosomes is dominated not only by microRNAs (miRNAs) but also by PIWI-interacting RNAs (piRNAs). We define a combined signature consisting of three miRNAs and three piRNAs that are suitable to detect AD with an AUC of 0.83 in a replication cohort and furthermore predict the conversion of mild\u2013cognitive impaired (MCI) patients to AD dementia with an AUC of 0.86 for the piRNA signature. When combining the smallRNA signature with pTau and A\u03b2 42\/40 ratio the AUC reaches 0.98. Our study reports a novel exosomal small noncoding RNA signature to detect AD pathology and provides the first evidence that in addition to miRNAs, piRNAs should also be considered as a candidate biomarker for AD.<\/jats:p>","DOI":"10.1038\/s41398-019-0579-2","type":"journal-article","created":{"date-parts":[[2019,10,7]],"date-time":"2019-10-07T12:02:51Z","timestamp":1570449771000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["A combined miRNA\u2013piRNA signature to detect Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"9","author":[{"given":"Gaurav","family":"Jain","sequence":"first","affiliation":[]},{"given":"Anne","family":"Stuendl","sequence":"additional","affiliation":[]},{"given":"Pooja","family":"Rao","sequence":"additional","affiliation":[]},{"given":"Tea","family":"Berulava","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9329-8912","authenticated-orcid":false,"given":"Tonatiuh","family":"Pena Centeno","sequence":"additional","affiliation":[]},{"given":"Lalit","family":"Kaurani","sequence":"additional","affiliation":[]},{"given":"Susanne","family":"Burkhardt","sequence":"additional","affiliation":[]},{"given":"Ivana","family":"Delalle","sequence":"additional","affiliation":[]},{"given":"Johannes","family":"Kornhuber","sequence":"additional","affiliation":[]},{"given":"Michael","family":"H\u00fcll","sequence":"additional","affiliation":[]},{"given":"Wolfgang","family":"Maier","sequence":"additional","affiliation":[]},{"given":"Oliver","family":"Peters","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5484-9710","authenticated-orcid":false,"given":"Hermann","family":"Esselmann","sequence":"additional","affiliation":[]},{"given":"Claudia","family":"Schulte","sequence":"additional","affiliation":[]},{"given":"Christian","family":"Deuschle","sequence":"additional","affiliation":[]},{"given":"Mathis","family":"Synofzik","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1492-5330","authenticated-orcid":false,"given":"Jens","family":"Wiltfang","sequence":"additional","affiliation":[]},{"given":"Brit","family":"Mollenhauer","sequence":"additional","affiliation":[]},{"given":"Walter","family":"Maetzler","sequence":"additional","affiliation":[]},{"given":"Anja","family":"Schneider","sequence":"additional","affiliation":[]},{"given":"Andre","family":"Fischer","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,10,7]]},"reference":[{"key":"579_CR1","first-page":"95","volume":"80","author":"A Fischer","year":"2014","unstructured":"Fischer, A. 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