Plasma TDP-43 is a potential biomarker for advanced limbic-predominant age-related TDP-43 encephalopathy neuropathologic change

Product:

CNS Disease Panel 120

Topic:

Neurology

Disease Area:

Dementia

Sample Type:

Plasma

Topic/Product:

CNS Disease Panel 120

Disease Area:

Dementia

Sample Type:

Plasma

Abstract

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a common cause of late-onset dementia that does not yet have specific in vivo biomarkers. Here, we examine the biomarker potential of plasma TDP-43, measured using a highly sensitive Nucleic Acid Linked Immuno-Sandwich Assay (NULISA), in detecting advanced LATE-NC. Leveraging plasma TDP-43 and phospho-TDP-43 data from 50 deceased Religious Orders Study and the Rush Memory and Aging Project participants, we show that plasma TDP-43 and pTDP-43 were associated with advanced LATE-NC, especially in those with comorbid Alzheimer’s disease neuropathologic change (ADNC): in the subgroup with autopsy-confirmed AD dementia (n=32), receiver operating characteristic area under the curve (AUC) for both plasma biomarkers approached 0.8. Plasma TDP-43 was also elevated in hippocampal sclerosis, a pathologic finding closely related to advanced LATE-NC. Together, our findings suggest the potential utility of plasma TDP-43 and pTDP-43 as biomarkers of LATE-NC, particularly in individuals with comorbid AD.

Authors & Affiliations

Jijing Wang1,2, Julie A. Schneider3, David A. Bennett3, Nicholas T. Seyfried4, Tracy L. Young-Pearse1,2, Hyun-Sik Yang1,2*

Department of Neurology, Brigham and Women’s Hospital, Boston, MA 02115, USA
Harvard Medical School, Boston, MA 02115, USA
Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA

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.