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Plasma Biomarkers of Neurodegeneration in Mild Cognitive Impairment with Lewy Bodies

Lookup NU author(s): Dr Calum Hamilton, Professor John O'Brien, Dr Rory Durcan, Dr Sarah Lawley, Nicola Barnett, Dr Gemma Roberts, Dr Michael FirbankORCiD, Professor John-Paul TaylorORCiD, Professor Alan ThomasORCiD

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


Abstract

Background Blood biomarkers of Alzheimer’s disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma Aβ42/40, p-tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another. Methods Plasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with a Simoa 4-plex assay for Aβ42, Aβ40, GFAP and NfL, and incorporated previously-collected p-tau181 from this same cohort. Results Probable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower Aβ42/40 (p = 0.06). GFAP and p-tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011). Conclusion Markers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p-tau181 in distinguishing MCI overall, and its subgroups, from healthy controls.


Publication metadata

Author(s): Hamilton CA, O'Brien JT, Heslegrave A, Laban R, Donaghy PC, Durcan R, Lawley S, Barnett NA, Roberts G, Firbank M, Taylor JP, Zetterberg H, Thomas AJ

Publication type: Article

Publication status: Published

Journal: Psychological Medicine

Year: 2023

Issue: ePub ahead of Print

Online publication date: 25/07/2023

Acceptance date: 23/06/2023

Date deposited: 26/06/2023

ISSN (print): 0033-2917

ISSN (electronic): 1469-8978

Publisher: Cambridge University Press

URL: https://doi.org/10.1017/S0033291723001952

DOI: 10.1017/S0033291723001952


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Funding

Funder referenceFunder name
101053962
2018-02532
ADSF-21-831376-C
ADSF-21-831377-C
201809-2016862
Alzheimer Drug Discovery Foundation, USA
ADSF-21-831381-C
ALFGBG-71320
Alzheimer’s Research UK
ARUK-PG2015-13Alzheimer`s Research UK
European Union Horizon 2020
JPND2021-00694
MR/W000229/1
MRC
NIHR
Swedish Research Council
UK Dementia Research Institute

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