Relation between Alpha-Synuclein and Core CSF Biomarkers of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is characterized by the presence of ß-amyloid plaques and neurofibrillary tangles, while Lewy body dementia (LBD) is characterized by α-synuclein (α-syn) inclusions. Some authors examine α-syn protein in the neurodegeneration process of AD and propose to consider cerebrospinal fluid (CSF) α-syn as a possible additional biomarker to the so-called "core" of AD. Objective: To determine whether there is a correlation between α-syn levels and "core" AD biomarkers in patients with mild cognitive impairment (MCI). Materials and methods: In total, 81 patients in the early stages of MCI were selected from the outpatient dementia consultation in Alicante General Hospital. Using a cross-sectional case-control design, patients were analyzed in four groups: stable MCI (MCIs; n = 25), MCI due to AD (MCI-AD; n = 32), MCI due to LBD (MCI-LBD; n = 24) and a control group of patients with acute or chronic headache (Ctrl; n = 18). Correlation between CSF protein levels in the different groups was assessed by the Rho Spearman test. Results: We found positive correlations between T-tau protein and α-syn (ρ = 0.418; p value < 0.05) and p-tau181p and α-syn (ρ = 0.571; p value < 0.05) exclusively in the MCI-AD group. Conclusion: The correlation found between α-syn and tau proteins in the first stages of AD support the involvement of α-syn in the pathogenesis of AD. This result may have clinical and diagnostic implications, as well as help to apply the new concept of "precision medicine" in patients with MCI.

Measurement of CSF α-synuclein improves early differential diagnosis of mild cognitive impairment due to Alzheimer's disease.

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/.

Frecuente alteración de la vía amiloide en la demencia con cuerpos de Lewy prodrómica / Frequent involvement of the amyloid pathway in prodromal dementia with Lewy bodis

Introducción. La demencia con cuerpos de Lewy (DCLW) es la más frecuente de las degenerativas, después de la enfermedad de Alzheimer. Objetivo. Analizar los biomarcadores core de la enfermedad de Alzheimer en el líquido cefalorraquídeo de pacientes exclusivamente hispanos con DCLW prodrómica, para conocer si existe alteración de la vía amiloide o de la vía tau. Pacientes y métodos. Entre 2008-2017 incluimos a 430 pacientes con deterioro cognitivo leve según los criterios de Petersen, procedentes de tres hospitales de la provincia de Alicante. Se les realizaron revisiones clínicas cada 6-12 meses para evaluar su estabilidad clínica o la progresión a demencia utilizando los criterios clínicos vigentes. Entre otras pruebas complementarias se analizaron los biomarcadores de enfermedad de Alzheimer en el líquido cefalorraquídeo. Resultados. Entre todos los pacientes incluidos, 26 desarrollaron DCLW y 29 se mantuvieron estables durante al menos cinco años, por lo que los consideramos como referencia. En este grupo solamente cinco (17%) tenían valores de proteína Abeta(1-42) inferiores a la normalidad, mientras que 16 (55%) de los pacientes con DCLW tenían niveles alterados. No se encontraron diferencias en los niveles de las proteínas tau. Al comparar los grupos con DCLW con y sin amiloidosis solamente encontramos diferencias en los niveles de proteína Abeta(1-42). Conclusiones. Destacamos la frecuente presencia de patología amiloidea en la DCLW prodrómica en nuestra población y la probable alteración de diferentes vías metabólicas en una misma demencia clínicamente definida

Introduction. Lewy body dementia (LBD) is the most frequent of the degenerative dementias, after Alzheimer’s disease. Aim. To analyse the core biomarkers of Alzheimer’s disease in the cerebrospinal fluid of exclusively Hispanic patients with prodromal LBD, in order to determine whether there is involvement of the amyloid pathway or the tau pathway. Patients and methods. Between 2008 and 2017 we included 430 patients with mild cognitive impairment according to Petersen criteria, from three hospitals in the province of Alicante. They underwent clinical check-ups every 6-12 months to evaluate their clinical stability or their progression to dementia using current clinical criteria. Among other complementary tests, biomarkers for Alzheimer's disease in the cerebrospinal fluid were analysed. Results. Of all the patients included, 26 developed LBD and 29 remained stable for at least five years, and were thus considered as a reference. In this group only five (17%) had Aβ1-42 protein values below normal, whereas 16 (55%) of the patients with LBD had altered levels. No differences were found in the levels of tau protein. On comparing the LBD groups with and without amyloidosis, differences were only found in the levels of Aβ1-42 protein. Conclusions. We highlight the frequent presence of amyloid pathology in prodromal LBD in our population, and the probable involvement of different metabolic pathways in the same clinically defined dementia