Alpha‐synuclein quantitative seed amplification assay predicts conversion to dementia

TL;DR

A new test called qnSAA can predict dementia risk by measuring alpha-synuclein levels in cerebrospinal fluid.

Contribution

The study introduces a quantitative version of the alpha-synuclein seed amplification assay (qnSAA) for improved dementia risk prediction.

Findings

qnSAA results correlate with cognitive performance and reflect biomarker progression over time.

Participants with fast qnSAA kinetics had a 75% chance of converting to dementia.

qnSAA can identify clinically relevant differences between patient populations at risk for dementia.

Abstract

The alpha‐synuclein seed amplification assay (SAA) has shown excellent performance in the detection of Lewy body pathology in cerebrospinal fluid (CSF). Lewy body pathology is prognostically relevant in patients at risk for dementia. Current assays only provide binary results, so there is a need to quantify the extent of pathology in living patients.

In addition to the “standard” SAA, we developed a quantitative SAA (qnSAA) and measured 432 CSF samples (216 baseline–follow‐up pairs).

qnSAA results correlated with cognitive performance. Seventy‐five percent of participants with fast qnSAA kinetics converted to dementia in the observed interval. Overall, participants with fast qnSAA kinetics accounted for 27.3% of dementia converters in the entire cohort.

Findings demonstrate promising properties of qnSAA measurements in a cohort of patients at risk for dementia. qnSAA results showed improved prognostic relevance and have potential to measure target engagement of therapies against Lewy body pathology.

In this study, we investigate the potential of a quantitative seed amplification assay (qnSAA) for alpha‐synuclein pathology in cerebrospinal fluid.The qnSAA can resolve clinically relevant differences between patient populations.qnSAA results change between baseline and follow‐up, reflecting biomarker progression.qnSAA results correlate with cognitive performance.qnSAA results allow identification of a patient population at 75% risk of converting to manifest dementia.

In this study, we investigate the potential of a quantitative seed amplification assay (qnSAA) for alpha‐synuclein pathology in cerebrospinal fluid.

The qnSAA can resolve clinically relevant differences between patient populations.

qnSAA results change between baseline and follow‐up, reflecting biomarker progression.

qnSAA results correlate with cognitive performance.

qnSAA results allow identification of a patient population at 75% risk of converting to manifest dementia.

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