ASC specks as a single-molecule fluid biomarker of inflammation in neurodegenerative diseases

Evgeniia Lobanova (), Yu P. Zhang, Derya Emin, Jack Brelstaff, Lakmini Kahanawita, Maura Malpetti, Annelies Quaegebeur, Kathy Triantafilou, Martha Triantafilou, Henrik Zetterberg, James B. Rowe, Caroline H. Williams-Gray, Clare Elizabeth Bryant and David Klenerman ()
Additional contact information
Evgeniia Lobanova: Lensfield Road
Yu P. Zhang: Lensfield Road
Derya Emin: Lensfield Road
Jack Brelstaff: University of Cambridge and Cambridge University Hospitals NHS Trust
Lakmini Kahanawita: University of Cambridge and Cambridge University Hospitals NHS Trust
Maura Malpetti: University of Cambridge and Cambridge University Hospitals NHS Trust
Annelies Quaegebeur: University of Cambridge and Cambridge University Hospitals NHS Trust
Kathy Triantafilou: Cardiff University
Martha Triantafilou: Cardiff University
Henrik Zetterberg: The Sahlgrenska Academy at the University of Gothenburg
James B. Rowe: University of Cambridge and Cambridge University Hospitals NHS Trust
Caroline H. Williams-Gray: University of Cambridge and Cambridge University Hospitals NHS Trust
Clare Elizabeth Bryant: University of Cambridge
David Klenerman: Lensfield Road

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Immunotherapeutic strategies for Alzheimer’s and Parkinson’s disease would be facilitated by better measures of inflammation. Here we established an ultra-sensitive single-molecule pull-down immunoassay combined with direct stochastic optical reconstruction microscopy (dSTORM) to measure the number, size and shape of individual extracellular inflammasome ASC specks. We assayed human post-mortem brain, serum and cerebrospinal fluid of patients with Parkinson’s and Alzheimer’s as well as healthy elderly. The number of ASC specks increased and showed altered morphology in the blood of early-stage Parkinson’s and Alzheimer’s patients compared to controls, mimicking those found in the brain and cerebrospinal fluid. In serum samples we also measured the number of Aβ, p-tau and α-syn aggregates and formed a composite biomarker of (ASC + p-tau)/Aβ and (ASC + α-syn)/Aβ ratios that distinguished age-matched healthy controls from patients with early-stage Alzheimer’s with AUC of 92% and early-stage Parkinson’s with AUC of 97%. Our findings confirm ASC specks as a fluid candidate biomarker of inflammation for neurodegenerative diseases with blood being the main focus for further development as convenient sample for diagnostics and clinical trials.

Date: 2024
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DOI: 10.1038/s41467-024-53547-0

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