The combined effect of amyloid-beta and tau biomarkers on brain atrophy in dementia with Lewy bodies

Background: Alzheimer's disease (AD)-related pathology is frequently found in patients with dementia with Lewy bodies (DLB). However, it is unknown how amyloid-beta and tau-related pathologies influence neurodegeneration in DLB. Understanding the mechanisms underlying brain atrophy in DLB can improve our knowledge about disease progression, differential diagnosis, drug development and testing of anti-amyloid and anti-tau therapies in DLB. Objectives: We aimed at investigating the combined effect of CSF amyloid-beta 42, phosphorylated tau and total tau on regional brain atrophy in DLB in the European DLB (E-DLB) cohort. Methods: 86 probable DLB patients from the E-DLB cohort with CSF and MRI data were included. Random forest was used to analyze the association of CSF biomarkers (predictors) with visual rating scales for medial temporal lobe atrophy (MTA), posterior atrophy (PA) and global cortical atrophy scale-frontal subscale (GCA-F) (outcomes), including age, sex, education and disease duration as extra predictors. Results: DLB patients with abnormal MTA scores had abnormal CSF A beta 42, shorter disease duration and older age. DLB patients with abnormal PA scores had abnormal levels of CSF A beta 42 and p-tau, older age, lower education and shorter disease duration. Abnormal GCA-F scores were associated with lower education, male sex, and older age, but not with any AD-related CSF biomarker. Conclusions: This study shows preliminary data on the potential combined effect of amyloid-beta and tau-related pathologies on the integrity of posterior brain cortices in DLB patients, whereas only amyloid-beta seems to be related to MTA. Future availability of a-synuclein biomarkers will help us to understand the effect of a-synuclein and AD-related pathologies on brain integrity in DLB.