How well do plasma Alzheimer's disease biomarkers reflect the CSF amyloid status?

Autor:	Hazan J; Division of Psychiatry, UCL, London, UK j.hazan@ucl.ac.uk., Abel E; UCL, UK Dementia Research Institute, London, UK., Rosa Grilo M; UCL Queen Square Institute of Neurology, London, UK., Alawode D; UCL, UK Dementia Research Institute, London, UK., Laranjinha I; UCL, UK Dementia Research Institute, London, UK., Heslegrave AJ; UCL, UK Dementia Research Institute, London, UK., Liu KY; UCL Division of Psychiatry, London, UK., Schott JM; Dementia Research Centre, Institute of Neurology, London, UK., Howard R; UCL Division of Psychiatry, London, UK., Zetterberg H; UCL, UK Dementia Research Institute, London, UK.; Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, Goteborg, Sweden., Fox NC; UCL, UK Dementia Research Institute, London, UK.; UCL Queen Square Institute of Neurology, London, UK.
Jazyk:	angličtina
Zdroj:	Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2024 Dec 18. Date of Electronic Publication: 2024 Dec 18.
DOI:	10.1136/jnnp-2024-334122
Abstrakt:	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. Competing Interests: Competing interests: HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics and Wave; has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk and Roche; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). NCF has served at scientific advisory boards and/or as a consultant for Biogen, Eisai, Ionis, Lilly, Roche/Genentech and Siemens. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
Databáze:	MEDLINE
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