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

Lobanova, Evgeniia, Zhang, Yu P., Emin, Derya, Brelstaff, Jack, Kahanawita, Lakmini, Malpetti, Maura, Quaegebeur, Annelies, Triantafilou, Kathy ORCID: https://orcid.org/0000-0002-7473-6278, Triantafilou, Martha ORCID: https://orcid.org/0000-0002-8489-2602, Zetterberg, Henrik, Rowe, James B., Williams-Gray, Caroline H., Bryant, Clare Elizabeth and Klenerman, David 2024. ASC specks as a single-molecule fluid biomarker of inflammation in neurodegenerative diseases. Nature Communications 15 , 9690. 10.1038/s41467-024-53547-0

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Research
ISSN:	2041-1723
Date of First Compliant Deposit:	12 November 2024
Date of Acceptance:	16 October 2024
Last Modified:	12 Nov 2024 12:15
URI:	https://orca.cardiff.ac.uk/id/eprint/173880

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