Measurement of CSF α‐synuclein improves early differential diagnosis of mild cognitive impairment due to Alzheimer’s disease

• Published in: Journal of neurochemistry 2019-07, Vol.150 (2), p.218-230
• Main Authors: García‐Ayllón, María‐Salud, Monge‐Argilés, José‐Antonio, Monge‐García, Victoria, Navarrete, Francisco, Cortés‐Gómez, Maria‐Angeles, Sánchez‐Payá, José, Manzanares, Jorge, Gasparini‐Berenguer, Ruth, Leiva‐Santana, Carlos, Sáez‐Valero, Javier
• Format: Article
• Language: English
• Subjects: Aged; alpha-Synuclein - cerebrospinal fluid; Alzheimer; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - complications; Alzheimer's disease; biomarker; Biomarkers; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Cognitive ability; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - etiology; Cross-Sectional Studies; Diagnosis; Diagnosis, Differential; Diagnostic systems; Differential diagnosis; Disease control; Early Diagnosis; Female; Humans; Impairment; Lewy bodies; Lewy body disease; Lewy Body Disease - diagnosis; Male; Middle Aged; mild cognitive impairment; Psychosis; Signs and symptoms; Synuclein; Tau protein; tau Proteins - cerebrospinal fluid; α‐synuclein
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.14719

Previous studies have indicated the potential of cerebrospinal fluid (CSF) α‐synuclein (α‐syn) to be an additional biomarker for improving differential diagnosis of Alzheimer’s disease (AD). We evaluated α‐syn diagnostic performance across a well‐characterized patient cohort with long‐term follow‐up. For this purpose, CSF α‐syn levels were determined in 25 subjects diagnosed with stable mild cognitive impairment (stable MCI; n = 25), 27 MCI cases due to AD (MCI‐AD; n = 32), 24 MCI cases due to Lewy body disease (MCI‐LBD; n = 24) and control subjects (Ctrl; n = 18). CSF α‐syn levels discriminate between the four groups. There were higher α‐syn levels in MCI‐AD patients and lower levels in MCI‐LBD patients. The combination of α‐syn and P‐tau resulted in a specificity of 99% and a sensitivity of 97% for MCI‐AD. MCI‐AD patients with early psychotic symptoms (n = 9) displayed a trend towards a decrease in P‐tau and α‐syn compared to the MCI‐AD patients without psychotic symptoms (n = 23). We conclude that adding CSF α‐syn to central core AD biomarkers improves an early differential diagnosis of MCI‐AD from other forms of MCI. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Previous studies suggest the potential of α‐synuclein (α‐syn) as a cerebrospinal fluid (CSF) biomarker for Alzheimer’s disease (AD). We aim to study the potential of CSF α‐syn for improving differential diagnosis of AD in the earliest period of clinical symptoms, at the stage of clinical mild cognitive impairment (MCI) diagnosis. Our findings indicate that CSF α‐syn improves the differential diagnosis of MCI cases due to AD compared to MCI due to Lewy body disease, but also with stable MCI patients and non‐disease control subjects. The combination of α‐syn and P‐tau resulted in specificity and sensitivity ≥ 97% for MCI‐AD. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/