Previous studies have indicated the potential of cerebrospinal fluid (CSF) a-synuclein (a-syn) to be an additional biomarker for improving differential diagnosis of Alzheimer's disease (AD). We evaluated a-syn diagnostic performance across a well-characterized patient cohort with long-term follow-up. For this purpose, CSF a-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 a-syn levels discriminate between the four groups. There were higher a-syn levels in MCI-AD patients and lower levels in MCI-LBD patients. The combination of a-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 a-syn compared to the MCI-AD patients without psychotic symptoms (n = 23). We conclude that adding CSF a-syn to central core AD biomarkers improves an early differential diagnosis of MCI-AD from other forms of MCI.

Objectives. To evaluate the association between apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) levels of Alzheimer's disease (AD) biomarkers and to study the influence of APOE genotype on the development of AD in a Spanish population. Material and Methods. The study comprised 29 amnestic mild cognitive impairment (MCI) patients and 27 control subjects. Using ELISA methodology, CSF biomarkers and tau/Aβ ratios were obtained. ANOVA and adjusted odds ratios were calculated. Results. We observed the effect of APOE genotype and age on CSF AD variables. The progression to AD was more clearly influenced by CSF AD variables than by age or APOE status. Conclusions. APOE status influences CSF AD variables. However, the presence of APOE ε4 does not appear to be a deterministic factor for the development of AD, because CSF variables have a greater influence on progression to the disease. These results confirm previous observations and, to our knowledge, are the first published in a Spanish population.

Background: Alzheimer’s disease (AD) is characterized by the presence of β-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.

The inclusion of the ratios in diagnostic criteria increases sensitivity and NPV for the diagnosis of MCI due to AD.

Background 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. Method 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). Levels of central core AD‐CSF biomarkers Aβ1‐42, T‐tau and P‐tau 181 were measured using enzyme‐linked immunosorbant assay (Innotest, Innogenetics/Fujirebio). Determination of α‐syn levels in CSF were performed using the LEGEND MAXTM human α‐synuclein ELISA kit (BioLegend). Result 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 P‐tau and α‐syn resulted in a specificity of 99% and a sensitivity of 97% for 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). Conclusion Adding CSF α‐syn to central core AD biomarkers improves an early differential diagnosis of MCI‐AD from other forms of MCI.