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A Longitudinal Study of Plasma ptau-181 in Mild Cognitive Impairment with Lewy Bodies and Alzheimer’s Disease

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Thomas, Alan J 
Hamilton, Calum A 
Heslegrave, Amanda 
Barker, Sally 
Durcan, Rory 



Background AD co-pathology is common in DLB and associated with increased decline. Plasma p-Tau181 is a blood-based biomarker which can detect AD co-pathology.

Objectives We investigated whether p-Tau181 was associated with cognitive decline in MCI with Lewy bodies (MCI-LB) and MCI with AD (MCI-AD).

Methods We assessed plasma p-Tau181 using a Single molecule array (Simoa) immunoassay at baseline and follow-up in a longitudinal cohort of MCI-LB, MCI-AD and controls.

Results One hundred and forty-six subjects (56 probable MCI-LB, 22 possible MCI-LB, 44 MCI-AD and 24 controls) were reviewed for up to 5.7 years. Probable MCI-LB had significantly higher p-Tau-181 (22.2% mean increase) compared with controls and significantly lower (24.4% mean decrease) levels compared with MCI-AD. ROC analyses of p-Tau-181 in discriminating probable MCI-LB from controls showed AUC of 0.68 (83% specificity, 57% sensitivity); for discriminating MCI-AD from healthy controls AUC was 0.8 (83.3% specificity, 72.7% sensitivity). P-Tau-181 concentration was less useful in discriminating between probable MCI-LB and MCI-AD: AUC of 0.64 (71.4% specificity, 52.3% sensitivity).

There was an association between p-Tau-181 and cognitive decline in MCI-AD but not in MCI-LB. In a subset with repeat samples there was a non-significant 3% increase per follow-up year in plasma p-Tau-181. The rate of change in p-Tau-181 was not significantly different in different diagnostic subgroups.

Conclusions p-Tau-181 was not associated with an increased decline assessed using either baseline or repeat p-Tau-181. P-Tau-181 partially discriminated probable MCI-LB from controls and MCI-AD from controls but was not useful at distinguishing probable MCI-LB from MCI-AD.



biomarkers, dementia with Lewy bodies, mild cognitive impairment, pTau181, plasma, Alzheimer Disease, Cognitive Dysfunction, Humans, Lewy Bodies, Lewy Body Disease, Longitudinal Studies

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Movement Disorders

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This work was supported by Alzheimer’s Research UK (ARUK-PG2015-13) and by the NIHR Newcastle Biomedical Research Centre. GE Healthcare provided the FP-CIT ligand for this investigator-led study. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), and the UK Dementia Research Institute at UCL.