P-tau/Aβ42 and Aβ42/40 Ratios in CSF Are Equally Predictive of Amyloid PET Status

Overview

Journal Alzheimers Dement (Amst)

Date 2021 May 24

PMID 34027020

Citations 34

Authors

Michelle R Campbell

Susan Ashrafzadeh-Kian

Ronald C Petersen

Michelle M Mielke

Jeremy A Syrjanen

Argonde C Van Harten

Val J Lowe

Clifford R Jack Jr

Joshua A Bornhorst

Alicia Algeciras-Schimnich

Affiliations

Soon will be listed here.

Abstract

Introduction: Measurement of amyloid beta (Aβ40 and Aβ42) and tau (phosphorylated tau [p-tau] and total tau [t-tau]) in cerebrospinal fluid (CSF) can be utilized to differentiate clinical and preclinical Alzheimer's disease dementia (AD) from other neurodegenerative processes.

Methods: CSF biomarkers were measured in 150 participants from the Mayo Clinic Study of Aging and the Alzheimer's Disease Research Center. P-tau/Aβ42 (Roche Elecsys, Fujirebio LUMIPULSE) and Aβ42/40 (Fujirebio LUMIPULSE) ratios were compared to one another and to amyloid positron emission tomography (PET) classification.

Results: Strong correlation was observed between LUMIPULSE p-tau/Aβ42 and Aβ42/40, as well as Elecsys and LUMIPULSE p-tau/Aβ42 and Aβ42/40 (Spearman's ρ = -0.827, -0.858, and 0.960, respectively). Concordance between LUMIPULSE p-tau/Aβ42 and Aβ42/40 was 96% and between Elecsys p-tau/Aβ42 and both LUMIPULSE ratios was 97%. All ratios had > 94% overall, positive, and negative percent agreement with amyloid PET classification.

Discussion: These data suggest that p-tau/Aβ42 and Aβ42/40 ratios provide similar clinical information in the assessment of amyloid pathology.

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References

Fox N, Black R, Gilman S, Rossor M, Griffith S, Jenkins L . Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology. 2005; 64(9):1563-72. DOI: 10.1212/01.WNL.0000159743.08996.99. View

Delaby C, Munoz L, Torres S, Nadal A, Le Bastard N, Lehmann S . Impact of CSF storage volume on the analysis of Alzheimer's disease biomarkers on an automated platform. Clin Chim Acta. 2018; 490:98-101. DOI: 10.1016/j.cca.2018.12.021. View

Morris J, Schindler S, McCue L, Moulder K, Benzinger T, Cruchaga C . Assessment of Racial Disparities in Biomarkers for Alzheimer Disease. JAMA Neurol. 2019; 76(3):264-273. PMC: 6439726. DOI: 10.1001/jamaneurol.2018.4249. View

Hampel H, OBryant S, Molinuevo J, Zetterberg H, Masters C, Lista S . Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic. Nat Rev Neurol. 2018; 14(11):639-652. PMC: 6211654. DOI: 10.1038/s41582-018-0079-7. View

Leinonen V, Alafuzoff I, Aalto S, Suotunen T, Savolainen S, Nagren K . Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B. Arch Neurol. 2008; 65(10):1304-9. DOI: 10.1001/archneur.65.10.noc80013. View

Cummings J . The Role of Biomarkers in Alzheimer's Disease Drug Development. Adv Exp Med Biol. 2019; 1118:29-61. PMC: 6750734. DOI: 10.1007/978-3-030-05542-4_2. View

Parnetti L, Eusebi P, Lleo A . Cerebrospinal Fluid Biomarkers for Target Engagement and Efficacy in Clinical Trials for Alzheimer's and Parkinson's Diseases. Front Neurol Neurosci. 2016; 39:117-23. DOI: 10.1159/000445452. View

Garrett S, McDaniel D, Obideen M, Trammell A, Shaw L, Goldstein F . Racial Disparity in Cerebrospinal Fluid Amyloid and Tau Biomarkers and Associated Cutoffs for Mild Cognitive Impairment. JAMA Netw Open. 2019; 2(12):e1917363. PMC: 6991300. DOI: 10.1001/jamanetworkopen.2019.17363. View

Alcolea D, Pegueroles J, Munoz L, Camacho V, Lopez-Mora D, Fernandez-Leon A . Agreement of amyloid PET and CSF biomarkers for Alzheimer's disease on Lumipulse. Ann Clin Transl Neurol. 2019; 6(9):1815-1824. PMC: 6764494. DOI: 10.1002/acn3.50873. View

10.

Cicognola C, Chiasserini D, Eusebi P, Andreasson U, Vanderstichele H, Zetterberg H . No diurnal variation of classical and candidate biomarkers of Alzheimer's disease in CSF. Mol Neurodegener. 2016; 11(1):65. PMC: 5013624. DOI: 10.1186/s13024-016-0130-3. View

11.

McKhann G, Knopman D, Chertkow H, Hyman B, Jack Jr C, Kawas C . The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3):263-9. PMC: 3312024. DOI: 10.1016/j.jalz.2011.03.005. View

12.

Kapaki E, Paraskevas G, Tzerakis N, Sfagos C, Seretis A, Kararizou E . Cerebrospinal fluid tau, phospho-tau181 and beta-amyloid1-42 in idiopathic normal pressure hydrocephalus: a discrimination from Alzheimer's disease. Eur J Neurol. 2007; 14(2):168-73. DOI: 10.1111/j.1468-1331.2006.01593.x. View

13.

Klunk W, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt D . Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol. 2004; 55(3):306-19. DOI: 10.1002/ana.20009. View

14.

Jack Jr C, Bennett D, Blennow K, Carrillo M, Dunn B, Budd Haeberlein S . NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018; 14(4):535-562. PMC: 5958625. DOI: 10.1016/j.jalz.2018.02.018. View

15.

Hansson O, Seibyl J, Stomrud E, Zetterberg H, Trojanowski J, Bittner T . CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts. Alzheimers Dement. 2018; 14(11):1470-1481. PMC: 6119541. DOI: 10.1016/j.jalz.2018.01.010. View

16.

Molinuevo J, Ayton S, Batrla R, Bednar M, Bittner T, Cummings J . Current state of Alzheimer's fluid biomarkers. Acta Neuropathol. 2018; 136(6):821-853. PMC: 6280827. DOI: 10.1007/s00401-018-1932-x. View

17.

Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K . Alzheimer's disease drug development pipeline: 2020. Alzheimers Dement (N Y). 2020; 6(1):e12050. PMC: 7364858. DOI: 10.1002/trc2.12050. View

18.

Soria Lopez J, Gonzalez H, Leger G . Alzheimer's disease. Handb Clin Neurol. 2019; 167:231-255. DOI: 10.1016/B978-0-12-804766-8.00013-3. View

19.

Campbell M, Ashrafzadeh-Kian S, Petersen R, Mielke M, Syrjanen J, Van Harten A . P-tau/Aβ42 and Aβ42/40 ratios in CSF are equally predictive of amyloid PET status. Alzheimers Dement (Amst). 2021; 13(1):e12190. PMC: 8129859. DOI: 10.1002/dad2.12190. View

20.

Shaw L, Hansson O, Manuilova E, Masters C, Doecke J, Li Q . Method comparison study of the Elecsys® β-Amyloid (1-42) CSF assay versus comparator assays and LC-MS/MS. Clin Biochem. 2019; 72:7-14. DOI: 10.1016/j.clinbiochem.2019.05.006. View