ASC specks as a single-molecule fluid biomarker of inflammation in neurodegenerative diseases
Year: 2024
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Institutions: University of Cambridge, UK Dementia Research Institute, Cambridge University Hospitals NHS Foundation Trust, University Hospital of Wales, Cardiff University, University of Wisconsin–Madison, Sahlgrenska University Hospital, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, University of Gothenburg, MRC Cognition and Brain Sciences Unit, Medical Research Council, Addenbrooke's Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: Wellcome Trust, Alzheimer's Society, National Institute for Health and Care Research, Parkinson's UK, Research Councils UK, University of Cambridge, University College London, European Commission, Cambridge University Hospitals, Vetenskapsrådet, UK Dementia Research Institute, HORIZON EUROPE Framework Programme, Medical Research Council, NIHR Cambridge Biomedical Research Centre
Awards: G1155019861, G1802301745, G2493601830, G2537968379, G2543812357, G2936052209, Fluid biomarkers for neurodegenerative dementias, Restoring brain function: from cortical microcircuits to complex behaviours in neurodegenerative disease., G3601207897, G3914690605, The NET-PDD study: defining the roles of NEuroinflammation and Tau aggregation in Parkinson's Disease Dementia, Bridging the gap: biophysical models of human frontotemporal lobar degeneration, G4260843567, G4377393254, G4753630297, G5040492720, MRC Transition Support Award: The NET-PDD study - defining the roles of NEuroinflammation and Tau aggregation in Parkinson's Disease Dementia, Fluid biomarkers for neurodegenerative dementias, G5760210149, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6158734006, G7434583919, G8979490183
OpenAlex ID: W4404224829