Cerebrospinal fluid α-synuclein seed amplification assay positivity is associated with increased plasma neurofilament light chain in Alzheimer's disease
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Updated: Jan 7, 2026
Detection of Disease-associated α-synuclein by Enhanced ELISA in the Brain of Transgenic Mice Overexpressing Human A53T Mutated α-synuclein
Published on: May 30, 2015
Giovanni Bellomo1, Andrea Toja2, Lorenzo Gaetani2
1Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; Department of Life Science, Health, and Health Professions, Link Campus University, Rome, Italy.
Background:
Synucleinopathy is the most common co-pathology in Alzheimer's disease (AD) and can be detected in vivo using cerebrospinal fluid (CSF) alpha-synuclein seed amplification assays (synSAA). CSF synSAA positivity has been linked to worse clinical outcome. This study investigated whether synSAA positivity is also associated with levels of plasma neurofilament light chain (NfL), a sensitive, unspecific marker of neurodegeneration.
Methods:
We retrospectively analyzed a cohort of 240 individuals across the AD clinical continuum who had undergone clinical, neuropsychological, and biomarker assessments including CSF synSAA. Analyses involving plasma NfL were conducted in the subgroup with available plasma samples collected at the time of lumbar puncture (n = 166). One-way and two-way ANOVA were used to compare log-transformed NfL levels among AD stages, according to synSAA status. Logistic regression models examined associations between log-transformed NfL and synSAA status, adjusting for age and AD stage.
Findings:
No significant age difference was found between synSAA-positive and negative groups. Plasma NfL levels were significantly higher in synSAA-positive individuals. This association remained significant after adjusting for age and AD clinical stage.
Interpretation:
In AD patients, CSF synSAA positivity is associated with increase of plasma NfL levels along the AD clinical continuum. This finding supports the knowledge that synuclein co-pathology represents a contributive factor of neurodegeneration in AD patients.
