--- title: "Plasma Cell-Free RNA Transcriptomics for AD and Related Dementias" id: "6830" type: "study" slug: "sa000052" published_at: "2024-07-01T05:16:00+00:00" modified_at: "2026-03-26T15:57:54+00:00" url: "https://dss.niagads.org/studies/sa000052/" markdown_url: "https://dss.niagads.org/studies/sa000052.md" excerpt: "Plasma samples were obtained from the Knight-ADRC and the Movement Disorder Clinic (MDC) at Washington University in Saint Louis repositories. These are deeply phenotyped cohorts, both clinically and molecularly with longitudinal data and samples available. The study leveraged plasma cfRNA..." --- ## Description Plasma samples were obtained from the Knight-ADRC and the Movement Disorder Clinic (MDC) at Washington University in Saint Louis repositories. These are deeply phenotyped cohorts, both clinically and molecularly with longitudinal data and samples available. The study leveraged plasma cfRNA of presymptomatic AD participants to capture the early changes caused by AD pathology and to build unbiased models that were able to balance a good performance with a scalable number of transcripts to facilitate potential clinical applications. We also evaluated the discriminative capabilities of the proposed AD presymptomatic models in the context of AD spectrum, PD, DLB, and FTD to ensure that the models were selectively capturing changes associated with AD pathobiology. This dataset includes 119 samples from healthy control participants without dementia, 65 samples from presymptomatic AD participants (CDR=0 at draw and current clinical diagnostic of AD), 42 samples from early symptomatic AD participants (CDR=0.5 at draw and current diagnostic of AD), and 50 samples from symptomatic AD (CDR=1 at draw, diagnostic of AD at draw, and current diagnostic of AD). All AD participants were required to have evidence of Aβ deposition (CSF Aβ<500ng/L), positive PET scan and/or evidence of clinical worsening measured by CDR from the time at draw to the last clinical visit. For 71 participants, timely matched CSF biomarker measurements and time at draw are available. Additionally, the dataset included participants from other neurodegenerative diseases: 17 DLB participants, 16 FTD participants, and 92 PD participants. AD, DLB, and FTD participants were diagnosed in accordance with clinical criteria that are embodied in the Uniform Data Set (UDS), the standard clinical data set that is collected in all participants who are enrolled in all of the 37-federally funded ADRCs. PD participants were clinically diagnosed according to the UK Brain Bank criteria. This research was conducted in accordance with the recommended protocols. Written informed consent was obtained from all participants or their family members. ## PI Laura Ibanez ibanezl@wustl.edu Washington University in St. Louis Juan A. Botia Universidad de Murcia ## Associated Datasets - [NG00142-Plasma Cell-Free RNA Transcriptomics for AD and Related Dementia](https://dss.niagads.org/datasets/ng00142/) This dataset includes 119 samples from healthy control participants without dementia, 65 samples from presymptomatic AD participants (CDR®=0 at draw and current clinical diagnostic of AD), 42 samples from early… [Learn more](https://dss.niagads.org/datasets/ng00142/) ## Associated Sample Sets - [snd10085 - Plasma Cell-Free RNA Transcriptomics](https://dss.niagads.org/sample-sets/snd10085/) 400 samples were sequenced using Illumina NovaSeq 6000 and Illumina HiSeq 2500. The dataset comprises raw sequencing data in FASTQ format and normalized gene counts for all samples. The normalized… [Learn more](https://dss.niagads.org/sample-sets/snd10085/) ## Cohorts - [Knight Alzheimer’s Disease Research Center (KGAD)](https://dss.niagads.org/cohorts/knight-alzheimers-disease-research-center-kgad/) The search for novel risk factors for Alzheimer disease relies on access to accurate and deeply phenotyped datasets. The Memory and Aging Project at the Knight-ADRC (Knight ADRC-MAP) collects plasma,… [Learn more](https://dss.niagads.org/cohorts/knight-alzheimers-disease-research-center-kgad/) - [The Movement Disorder Clinic (MDC)](https://dss.niagads.org/cohorts/the-movement-disorder-clinic-mdc/) The Movement Disorder Clinic (MDC) at Washington University in Saint Louis (St. Louis, MO, USA) recruits and assess longitudinally participants with movements disorders. The Genetics of the Parkinson's Disease study… [Learn more](https://dss.niagads.org/cohorts/the-movement-disorder-clinic-mdc/) ## Grants This work was supported by grants from the National Institutes of Health K99/R00-AG062723 (LI), R01AG044546 (CC), P01AG003991, RF1AG053303 (CC), R01AG058501 (CC), RO1 NS075321 (JSP), U01AG058922 (CC), P30 AG066444 (JCM), P01 AG03991 (JCM), and P01 AG026276 (JCM), the Michael J Fox Foundation (LI/CC), the Alzheimer’s Drug Discovery Foundation (LI), Bright Focus Foundation (LI), and the Department of Defense (LI). AC was supported by the Science and Technology Agency, Séneca Foundation, Comunidad Autónoma Región de Murcia, Spain through the Grant [20762/FPI/18]. ## Acknowledgement ### Acknowledgment statement for any data distributed by NIAGADS: Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging. ### For investigators using Plasma Cell-Free RNA Transcriptomics for AD and Related Dementias data: We thank all the participants and their families along with the institutions and all the staff who provided plasma tissue, without whom this study would not have been possible. This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, the Neurogenomics and Informatics Center (NGI: [https://neurogenomics.wustl.edu/](https://neurogenomics.wustl.edu/) ) and the Departments of Neurology and Psychiatry at Washington University School of Medicine. ## Publications - Cisterna-García A. **Cell-free RNA signatures predict Alzheimer's disease.***iScience. 2023 Dec 15.*[PubMed link](https://pubmed.ncbi.nlm.nih.gov/38089583/)