Prognostic value of plasma brain-derived pTau

Product:

CNS Disease Panel 120

Topic:

CNS

Disease Area:

Alzheimer's Disease

Sample Type:

Plasma

Topic/Product:

CNS Disease Panel 120

Disease Area:

Alzheimer's Disease

Sample Type:

Plasma

Abstract

Background Plasma brain-derived pTau217 (BD-pTau217) may provide a Alzheimer’s disease-specific plasma tau measure than total pTau217, but its prognostic value is unclear. We compared BD-pTau217 and total plasma pTau217 for predicting clinical and amyloid PET progression in cognitively unimpaired (CU) ADNI participants.

Methods Plasma NULISAseq biomarkers were measured in 1,427 ADNI participants, including 529 CU individuals. Amyloid PET progression was assessed in baseline CU amyloid-negative participants (Centiloid ≥24.1) with longitudinal PET imaging; clinical progression was assessed in all baseline CU participants. Associations were evaluated using Cox models and time-dependent AUC.

Results BD-pTau217 did not clearly outperform total pTau217 for predicting progression to mild cognitive impairment or dementia. However, among baseline amyloid-negative participants (N=175), BD-pTau217 better predicted amyloid PET positivity at 2.5 years (tdAUC 0.82 vs 0.69; HR=10.54, p=0.00015) and 4 years (tdAUC 0.77 vs 0.64; HR=7.03, p=0.00055).

Conclusion BD-pTau217 improved prediction of near-term amyloid PET progression, with less clear advantage for clinical progression.

BD-pTau217 predicted amyloid PET progression in CU ADNI participants.
BD-pTau217 outperformed total pTau217 at the CL ≥24.1 threshold.
BD-pTau217 and total pTau217 performed similarly for clinical progression.
Prognostic performance varied across amyloid PET thresholds.
BD-pTau217 may support risk stratification in prevention trials.

Authors & Affiliations

Valentina Ghisays¹, Marisa N. Denkinger², Alpana Singh², Tainá M. Marques², Michael Malek-Ahmadi¹, Kendall Van-Keuren Jensen³, Hillary D. Protas¹, Javad Sohankar¹, Dhruman D. Goradia¹, Vivek Devadas¹, Yinghua Chen¹, Shan Li¹, Jessica B. Langbaum¹, Michael W. Weiner⁴, Eric M. Reiman¹, Yi Su¹, Nicholas J. Ashton¹˒²˒⁵*, and Alzheimer’s Disease Neuroimaging Initiative
¹ Banner Alzheimer’s Institute, Phoenix, AZ, USA
² Banner Sun Health Research Institute, Sun City, AZ, USA
³ Translational Genomics Research Institute, Phoenix, Arizona, USA
⁴ University of California San Francisco, San Francisco, CA, USA
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
* Corresponding author

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition. He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.