Year: 2024
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Can plasma biomarkers as well as cerebrospinal fluid (CSF) perform in the separation of amyloid-beta-positive (Aβ+) vs amyloid-beta-negative (Aβ-) groups across an age range seen in an NHS cognitive disorder clinic? METHODS: As part of the routine diagnostic investigation of 111 clinic patients who had contemporaneous blood and CSF samples taken, patients were categorised into Aβ+ and Aβ- groups based on their CSF in an Aβ42/40 ratio. We then evaluated four single molecule array (Simoa) Quanterix assays, quantifying single plasma analytes and ratios (p-tau217, p-tau217/Aβ42 ratio, p-tau181, p-tau181/Aβ42 ratio and Aβ42/40 ratio) in their ability to distinguish between these groups and the effect of age. RESULTS: The median (range) age of participants was 66 (55-79) years with 48 females (43.2%). The areas under the curve (AUC), not accounting for age, for the ability to discriminate Aβ+ from Aβ- groups were plasma p-tau217 AUC=0.94, Aβ42/40 AUC=0.78 and p-tau181 AUC=0.77. Combining p-tau217/Aβ42 increased the AUC to 0.97. The difference between the groups was influenced by age with less separation in older individuals: a significant negative interaction term between age and group for plasma p-tau217 concentrations (-0.037, p=0.013) and p-tau217/Aβ42 ratio (-0.007, p=0.008). CONCLUSIONS: There was variable performance of plasma biomarkers to recapitulate the CSF assay. Both p-tau217 and p-tau217/Aβ42 showed excellent promise as surrogates of CSF amyloid status, although with slightly reduced performance in older individuals. There was poorer discriminatory ability for p-tau181 and Aβ42/40. Further research is needed to address potential age-related confounds.
Authors: Jemma Hazan, Emily Abel, Miguel Rosa Grilo, Deborah Alawode, Ines Laranjinha, Amanda J Heslegrave, Kathy Y Liu, Jonathan M Schott, Robert Howard, Henrik Zetterberg, Nick C Fox
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Stiftelsen för Gamla Tjänarinnor, EU Joint Programme – Neurodegenerative Disease Research, National Institute for Health and Care Research, European Commission, Rosetrees Trust, Hjärnfonden, Vetenskapsrådet, University College London Hospitals NHS Foundation Trust, UK Dementia Research Institute, HORIZON EUROPE Framework Programme, Medical Research Council
Awards: G1057200632, G1088883541, G150733400, G1551449788, G1588116593, G1771944843, G1802301745, G1833008592, G201353144, G2057385626, G220789858, G237833635, G2543812357, G2799940023, G292763017, G3241251457, Fluid biomarkers for neurodegenerative dementias, G3903502641, G3914690605, G4234328627, G4260843567, G432431387, G434337789, G5040492720, G506008078, G516766298, Fluid biomarkers for neurodegenerative dementias, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6158734006, G6289970089, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6745400708, G691317373, Does the central noradrenergic system play a role in agitation in Alzheimer's disease?
OpenAlex ID: W4405527832