- March 14, 2026
- Benoit Lehallier, et al., Alkahest
Topic/Product:
CNS Disease Panel 120
Disease Area:
Parkinson's Disease
Sample Type:
Plasma
Abstract
Many diseases begin developing years before symptoms appear1–3, yet biospecimens from these early stages are rarely available. We developed Chronos, a framework that uses privacy-preserving tokenization4 to link archived plasma samples with longitudinal clinical records, enabling the modeling of molecular trajectories across time. Starting with >100 million archived, routine-donation samples from 3 million plasma donors, we assembled a longitudinal Parkinson’s disease cohort and profiled 2,609 samples from 348 cases and 348 matched controls using four proteomics platforms, covering more than 25,000 proteoforms. We reproduced proteomic signatures from clinically-phenotyped cohorts and revealed early, coordinated alterations in a CXCL12, cell ratios to predict future diagnosis, achieving a maximum cross-validated area under the curve of 0.76 and replicated the findings in up to 5 independent cohorts. Chronos enables disease detection before clinical manifestation by prioritizing longitudinal molecular changes over symptoms, and provides a general framework to reconstruct chronic and acute disease trajectories from large plasma collections.
Authors & Affiliations
Chunmiao Feng* ¹, Idit Kosti* ¹, Yuelong Guo¹, Ying Wang¹, Nathan S. Watson-Haigh¹, Balint File¹, Nhi Hin¹, Tibor Nanasi¹, Jingyu Guo¹, Rad Suchecki¹, Rick Tearle¹, Kathleen Koborsi¹, Kim Dang¹, Rashi Saxena¹, Arnaud Teichert¹, Shalini Padmanabhan², Brit Mollenhauer³⁴, Samuel M. Goldman⁵, Tony Wyss-Coray⁶⁷⁸, Karoly Nikolich¹⁹, Scott Lohr¹, and Benoit Lehallier¹
¹ Alkahest, Inc., San Carlos, CA, USA
² The Michael J. Fox Foundation for Parkinson’s Research, New York, NY, USA
³ Department of Neurology, University Medical Center Goettingen, Goettingen, Germany
⁴ Paracelsus-Elena-Klinik, Kassel, Germany
⁵ Division of Occupational, Environmental, and Climate Medicine, University of California San Francisco, San Francisco, CA, USA
⁶ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA
⁷ The Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, California, USA
⁸ Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA
⁹ Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA
* Equal Contribution