Investigating alpha-synuclein co-pathology in Alzheimer's disease by means of cerebrospinal fluid alpha-synuclein seed amplification assay

INTRODUCTIONLewy body disease, a frequently observed co-pathology in Alzheimer's disease (AD), can be identified antemortem in cerebrospinal fluid (CSF) by alpha-synuclein seed amplification assay (alpha S-SAA). The prevalence and clinical impact of CSF alpha S-SAA positivity in AD are still unknown.METHODS alpha S-SAA was performed on CSF samples from 240 AD patients (preclinical, prodromal, and dementia stages), 85 controls, 84 patients with Parkinson's disease (PD), and 21 patients with PD with dementia or dementia with Lewy bodies. In AD patients, associations between alpha S-SAA positivity and cognitive changes were also evaluated.RESULTSIn agreement with available neuropathological studies, alpha S-SAA positivity was observed in 30% of AD patients (vs 9% in controls), and was associated with cognitive decline, visuospatial impairment, and behavioral disturbances.DISCUSSION alpha S-SAA positivity in AD patients reflects the prevalence observed in neuropathological series and is associated with a worse clinical outcome. These data confirm the validity of CSF alpha S-SAA positivity as biomarker of synucleinopathy.