Blood biomarkers are becoming increasingly important for clinical trial stratification and healthcare. Therefore this work explored these existing markers’ diagnostic accuracy and ability to differentially diagnose Dementia with Lewy Bodies (DLB) from Alzheimer’s Disease (AD). A multi-modal, combinatorial approach was taken to validate plasma and PET imaging markers’ utilities.The singular and combined ability of two emerging phospho-tau markers, p-tau217 and p-tau231, to differentiate DLB from AD was tested in a well-characterised cohort of patients over the age of 50. Following from this, plasma Glial Fibrillary Acidic Protein (GFAP) was introduced into the analyses to explore its association with these phospho-tau markers and assess whether its addition to predictive models could improve differential diagnostic accuracy. As a marker of astrogliosis, plasma GFAP’s associations with microglial activation in brain regions of interest was then assessed using [11C]PK11195 PET imaging data. Finally, an array of univariate statistical analyses were performed to analyse the significance of this data. Receiver operator characteristic (ROC) curves were generated for the plasma and neuroimaging data to compare their diagnostic abilities with area under curve (AUC) calculations. Finally, these blood and imaging biomarkers were subject to Akaike Inclusion Criteria (AIC) testing to see which of the additive biomarker models generated were most successful at predicting DLB diagnoses.