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The relationship between plasma biomarkers and amyloid PET in dementia with Lewy bodies

Lookup NU author(s): Dr Paul Donaghy, Dr Michael FirbankORCiD, Dr George Petrides, Nicola Barnett, Kirsty OlsenORCiD, Professor Nicola HeslehurstORCiD, Professor Alan ThomasORCiD, Professor John O'Brien

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Introduction Amyloid-β (Aβ) deposition is common in dementia with Lewy bodies (DLB) and has been associated with more rapid disease progression. An effective biomarker that identified the presence of significant brain Aβ in people with DLB may be useful to identify and stratify participants for research studies and to inform prognosis in clinical practice. Plasma biomarkers are emerging as candidates to fulfil this role. Methods Thirty-two participants with DLB had brain amyloid (18F-florbetapir) PET, of whom 27 also had an MRI to enable the calculation of 18F-florbetapir SUVR. Plasma Aβ42/40, phosphorylated tau (ptau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) were measured using single molecule array (Simoa). The plasma biomarkers were investigated for correlation with 18Fflorbetapir SUVR, discriminant ability to identify Aβ-positive cases based on a predefined SUVR threshold of 1.10 and correlation with subsequent cognitive decline over one year. Results All four plasma markers significantly correlated with 18F-florbetapir SUVR (|β|=.40-.49; p<.05). NfL had the greatest area under the receiver operating characteristic curve to identify Aβ-positive cases (AUROC .84 (95% CI .66, 1); β=.46, p=.001), whereas Aβ42/40 had the smallest (AUROC .73 (95% CI .52, .95); β=-.47, p=.01). Accuracy was highest when combining all four biomarkers (AUROC .92 (95% CI .80, 1)). Lower plasma Aβ42/40 was significantly associated with more rapid decline in cognition (β=.53, p<.01). Conclusions Plasma biomarkers have the potential to identify Aβ deposition in DLB. Further work in other cohorts is required to determine and validate optimal cut-offs for these biomarkers.


Publication metadata

Author(s): Donaghy PC, Firbank M, Petrides G, Lloyd J, Barnett N, Olsen K, Heslegrave A, Zetterberg H, Thomas AJ, O'Brien JT

Publication type: Article

Publication status: Published

Journal: Parkinsonism and Related Disorders

Year: 2022

Volume: 101

Pages: 111-116

Print publication date: 01/08/2022

Online publication date: 19/07/2022

Acceptance date: 17/07/2022

Date deposited: 01/08/2022

ISSN (print): 1353-8020

ISSN (electronic): 1873-5126

Publisher: Elsevier

URL: https://doi.org/10.1016/j.parkreldis.2022.07.008

DOI: 10.1016/j.parkreldis.2022.07.008


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Funding

Funder referenceFunder name
BH120812

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