Multiplex plasma profiling of synaptic biomarkers in Alzheimer’s disease using NULISA: early alterations, APOE genotype effects, and pTau217 associations

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

INTRODUCTION

Synaptic markers are altered in the CSF of Alzheimer’s disease (AD) patients, but their quantification in plasma remains challenging. We evaluated plasma synaptic markers in MCI and mild AD using the nucleic acid–linked immuno-sandwich assay (NULISA) and their correlation with APOE genotype.

METHODS

272 participants (154 CSF-confirmed AD, 118 controls) underwent plasma assessment with the NULISA CNS panel. A subset (n=48) also had CSF measurements. Analyses were adjusted for age, sex, comorbidity, and renal function.

RESULTS

NULISA revealed plasma alterations in NPTX2, NPTXR, SNAP-25, and VSNL1 in AD, with SNAP-25 and NPTXR already altered at MCI stage. APOE ε4/ε4 carriers showed higher plasma SNAP-25. Plasma SNAP-25 and NPTXR correlated positively with pTau217. No plasma-CSF concordance was observed.

DISCUSSION

NULISA identifies plasma synaptic biomarker alterations in early AD, with APOEε4 influencing SNAP-25 levels. Associations with pTau217 suggest a link between synaptic damage and tau phosphorylation. Longitudinal studies are warranted.

Authors and Affiliations

C. Martinuzzo 1-4 and A. Pilotto1-5 , C. Tolassi 1-3 , M. Sauer7, A. L. Benedet7, A. Rondina 1-4, A. Galli 1-4, T. Merati 1-4, C. Trasciatti 1-4, I. Girotto 1-3, G. di Molfetta7, I. Pola7, K. Tan7, W. Traichel7, S. Caratozzolo1,2, S. Pelucchi6, E. Marcello6, F. Gardoni6, M. Di Luca6, H. Zetterberg7-13, N. J Ashton7, 14-15 and A. Padovani1-4, 16

1 Department of Continuity of Care and Frailty, Neurology Unit, ASST Spedali Civili Brescia University Hospital, Brescia, Italy
2 Neurobiorepository and Laboratory of advanced biological markers, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy
3 Laboratory of digital Neurology and biosensors, University of Brescia, Italy
4 Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Italy
5 Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institute, Sweden
6 Department of Pharmacological and Biomolecular Sciences, “Rodolfo Paoletti”, University of Milan, Milan, Italy
7 Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
8 Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
9 Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
10 Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
11 Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK
12 UK Dementia Research Institute at UCL, London,
13 UK Centre for Brain Research, Indian Institute of Science, Bangalore, India
14 Banner Alzheimer’s Institute and University of Arizona, Phoenix, AZ, USA
15 Banner Sun Health Research Institute, Sun City, AZ 85351, USA
16 Brain Health Center, University of Brescia, Brescia, Italy

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.