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.