Aims

Plasma phosphorylated tau181 (ptau181) levels are been associated with amyloid-β deposition in Alzheimer’s disease (AD). Lewy body disease (LBD) frequently presents with amyloid-β co-pathology, which influences disease progression, cognitive decline, and brain atrophy.

We aimed to evaluate whether plasma ptau181 helps to identify amyloid-β co-pathology in the LBD spectrum, and whether plasma ptau181 levels in LBD are associated with AD cerebrospinal fluid (CSF) biomarkers.

Methods

We selected 203 Stanford research participants: 97 healthy controls, 37 Parkinson’s disease with normal cognition, 39 on the LBD-spectrum (25 MCI-LB and 14 dementia-LB), and 30 on the AD-spectrum (10 MCI-AD and 20 dementia-AD). Plasma ptau181 concentrations were measured using the Lumipulse G fully automated platform from Fujirebio Diagnostics. Diagnostic accuracy was evaluated with area-under-the-curve (AUC) values from receiver-operating characteristic (ROC) analyses.

Results

Plasma ptau181 levels predicted amyloid-β positivity in LBD patients (AUC=0.726). Combining plasma ptau181 levels with age, sex, years of education, APOE e4 genotype, and global cognition (MoCA), improved the prediction of amyloid-β positivity (AUC= 0.881). Similarly, plasma ptau181 levels predicted amyloid-β positivity in MCI-LB patients (AUC=0.691). This model was improved by including age, sex, years of education, APOE E4 genotype, and MoCA (AUC=0.826).

Plasma ptau181 levels were negatively associated with CSF Aβ42/Aβ40 ratio and positively associated with CSF ptau181/Aβ40 ratio. There were no differences in plasma ptau181 levels between the sexes. There was no association between plasma ptau181 levels with age, years of education, MoCA, or functional assessment measured with CDR.

Conclusions

Plasma ptau181 levels help to identify LBD patients with amyloid-β co-pathology and are associated with AD CSF biomarkers, even at the prodromal MCI stage. These findings support the use of plasma ptau181 as a screening tool for amyloid-β co-pathology in LBD.