Strong diagnostic performance of plasma ptau217 for CSF biomarker-defined young-onset Alzheimer disease in a diagnostically heterogeneous clinical cohort.

Autor:	Eratne D; Neuropsychiatry, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3052, Australia. deratne@unimelb.edu.au.; Department of Psychiatry, University of Melbourne, Grattan St, Parkville, Melbourne, VIC, 3052, Australia. deratne@unimelb.edu.au.; The Florey Institute, 30 Royal Parade, Parkville, VIC, 3052, Australia. deratne@unimelb.edu.au., Li QX; The Florey Institute, 30 Royal Parade, Parkville, VIC, 3052, Australia., Lewis C; Department of Psychiatry, University of Melbourne, Grattan St, Parkville, Melbourne, VIC, 3052, Australia., Dang C; Department of Psychiatry, University of Melbourne, Grattan St, Parkville, Melbourne, VIC, 3052, Australia.; National Ageing Research Institute, 34-54 Poplar Rd, Parkville, VIC, 3052, Australia., Kang MJY; Neuropsychiatry, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3052, Australia.; Department of Psychiatry, University of Melbourne, Grattan St, Parkville, Melbourne, VIC, 3052, Australia., Grewal J; The Alfred Hospital, 55 Commercial Rd, Melbourne, VIC, 3004, Australia., Loi S; Neuropsychiatry, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3052, Australia.; Department of Psychiatry, University of Melbourne, Grattan St, Parkville, Melbourne, VIC, 3052, Australia., Walterfang M; Neuropsychiatry, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3052, Australia.; Department of Psychiatry, University of Melbourne, Grattan St, Parkville, Melbourne, VIC, 3052, Australia.; The Florey Institute, 30 Royal Parade, Parkville, VIC, 3052, Australia., Evans AH; Neuropsychiatry, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3052, Australia., Malpas CB; Department of Medicine, Royal Melbourne Hospital, Grattan St, Parkville, Melbourne, VIC, 3052, Australia.; University of Melbourne, Grattan St Parkville VIC 3052, Melbourne, Australia., Pedrini S; Edith Cowan University, Joondalup, 6027, Australia., Martins R; Edith Cowan University, Joondalup, 6027, Australia.; Macquarie Medical School, Macquarie University, Balaclava Rd, Macquarie Park, NSW, 2109, Australia., Chatterjee P; The Florey Institute, 30 Royal Parade, Parkville, VIC, 3052, Australia., Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Universitetsplatsen 1, 405 30, Gothenburg, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 43180, Mölndal, Sweden.; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.; UK Dementia Research Institute at UCL, London, WC1N 3BG, UK., Blennow K; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Universitetsplatsen 1, 405 30, Gothenburg, Sweden., Berkovic SF; Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Grattan St, Parkville, VIC, 3052, Australia., Santillo AF; Department of Clinical Sciences, Clinical Memory Research Unit, Faculty of Medicine, Lund University, 221 00, Malmö, Sweden., Collins S; The Florey Institute, 30 Royal Parade, Parkville, VIC, 3052, Australia., Masters CL; The Florey Institute, 30 Royal Parade, Parkville, VIC, 3052, Australia., Velakoulis D; Neuropsychiatry, Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3052, Australia.; Department of Psychiatry, University of Melbourne, Grattan St, Parkville, Melbourne, VIC, 3052, Australia.
Jazyk:	angličtina
Zdroj:	Journal of neurology [J Neurol] 2024 Dec 12; Vol. 272 (1), pp. 25. Date of Electronic Publication: 2024 Dec 12.
DOI:	10.1007/s00415-024-12732-3
Abstrakt:	Objective: We investigated diagnostic utility of phosphorylated tau 217 and 181 (ptau217, ptau181), glial fibrillary acidic protein (GFAP), amyloid beta 42 and 40 (Aβ42, Aβ40), and neurofilament light (NfL) to distinguish biomarker-defined Alzheimer disease (AD) from non-AD conditions, in a heterogenous clinical cohort of younger people. Methods: Plasma biomarkers were analysed using ultrasensitive technology, and compared in patients with CSF Alzheimer disease profiles (A+T+) to other CSF profiles (Other). Results: Seventy-nine patients were included, median age 60.8 years: 16 A+T+, 63 Other. Ptau217, ptau181, GFAP were significantly elevated in A+T+ compared to Other (3.67 vs 1.12 pg/mL, 3.87 vs 1.79 pg/mL, 189 vs 80 pg/mL, respectively). ptau217 distinguished AD from Other with 90% accuracy (88% specificity, 100% sensitivity). ptau217 also demonstrated strong diagnostic performance for clinically diagnosed AD. Conclusions: Plasma ptau217 has strong diagnostic performance in distinguishing CSF biomarker-defined AD in a clinically relevant, younger cohort of people with symptoms, adding further weight for a simple diagnostic blood test for AD as a cause of a patient's symptoms. Competing Interests: Declaration of interests and financial disclosures: 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). SL has received honorarium from Lundbeck and Otsuka. AHE has received honoraria from Abbvie, STADA, Seqirus, and Ipsen. KB has served as a consultant and at advisory boards for Abbvie, AC Immune, ALZPath, AriBio, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. All the other authors have nothing to disclose. Statistical analysis conducted by: Dr Dhamidhu Eratne. Consent statement: All human subjects provided informed consent. (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze:	MEDLINE
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