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α-Synuclein seed amplification assay in Lewy body dementia versus Alzheimer's disease
Oskar H McWilliam1, Remarh Bsoul2, Eva L Lund2,3
1Danish Dementia Research Centre Department of Neurology Copenhagen University Hospital - Rigshospitalet Copenhagen Denmark.
Introduction:
Differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) is challenging. Seed amplification assay (SAA) is sensitive for the detection of misfolded α-synuclein.
Methods:
Patients with DLB (N = 31) and AD (N = 25) were recruited and evaluated. Misfolded α-synuclein was assessed in cerebrospinal fluid (CSF), skin, urine, and olfactory mucosa using SAA.
Results:
The accuracy of α-synuclein-SAA for DLB was 87% (95% confidence interval [CI]: 77% to 98%) in CSF, 85% (95% CI: 75% to 98%) in skin, 58% (95% CI: 47% to 69%) in olfactory mucosa, and 59% (95% CI: 51% to 66%) in urine. The core symptoms - fluctuations, REM sleep behavior disorder, and parkinsonism - had accuracies for SAA positivity of ≥79%. Notably, 95% of SAA-positive patients also had hyposmia.
Discussion:
These findings support the use of CSF and skin α-synuclein-SAAs as diagnostic tools for DLB, with strong associations between SAA and clinical phenotype. In particular, intact olfactory function is associated with a lower risk of SAA positivity.
Highlights:
CSF and skin biopsies show high diagnostic accuracy for α-synuclein, demonstrating good concordance.Strong correlations exist between core symptoms of DLB and pathological α-synuclein.A very high sensitivity of hyposmia for pathological α-synuclein is observed.A novel proof-of-concept is offered for the potential detection of pathological α-synuclein in urine, marking the first such comparative analysis between patients with DLB and AD.
