CSF alpha-synuclein aggregates by seed amplification and clinical presentation of AD

INTRODUCTION: Accumulating evidence suggests that a-synuclein (aSyn) can modulate Alzheimer ' s disease (AD) pathology. The aim of this study was to evaluate the prevalence and clinical features associated with cerebrospinal fluid (CSF) aSyn detected by seed amplification assay (SAA) in AD.METHODS: Eighty AD patients with CSF AT(N) biomarker positivity (mean age 70.3 +/- 7.3 years) and 28 non-AD age-matched controls were included. All subjects underwent standardized clinical assessment; CSF aSyn aggregates were detected by SAA.RESULTS: CSF was aSyn-SAA positive (aSyn+) in 36/80 AD patients (45%) and in 2/28 controls (7.1%). AD aSyn+ and aSyn- patients were comparable for age, disease severity, comorbidity profile, and CSF core biomarkers. AD aSyn+ presented a higher prevalence of atypical phenotypes and symptoms.CONCLUSIONS: Our findings demonstrate that concomitant CSF aSyn pathology is present in a significant proportion of AD patients starting in the early stages and can affect clinical presentation. Longitudinal studies are warranted to evaluate the significance for the disease course.