Relation between alpha‐synuclein and core CSF biomarkers in Alzheimer's disease: Biomarkers (non‐neuroimaging) / Novel biomarkers

Background Up to 50% of Alzheimer´s disease (AD) cases exhibit significant Lewy bodies (LB) pathology in addition to plaques and tangles. It has been hypothesized that Aβ, tau and alpha‐synuclein (α‐syn) proteins promote the accumulation of one another. We evaluated the relation between those CSF proteins in a well‐characterized patient mild cognitive impairment (MCI) cohort. Method Between 2010‐2015, we included 81 MCI patients (Petersen criteria 2006) from the out‐patient consultation of Neurology Service in University General Hospital of Alicante and 18 control subjects. After a long term follow‐up (mean: 53 months), 25 patients were diagnosed with stable MCI, 32 MCI due to AD (MCI‐AD) and 24 MCI due to Lewy body dementia (MCI‐LBD). Levels of central core AD‐CSF biomarkers Aβ1‐42 (Aβ42), T‐tau (total‐tau) and P‐tau [phospho‐tau (181P)] were measured using ELISA (Innotest, Innogenetics/Fujirebio). Determination of α‐syn levels in CSF were performed using the LEGEND MAX TM human α‐synuclein ELISA kit (BioLegend, San Diego, USA). Rho of Spearman correlation coefficients among CSF protein levels were evaluated. Result CSF α‐syn significantly positively correlated with T‐tau (Rho= 0.41, p=0.17 ) and P‐tau (Rho=0.57, p=0.001) exclusively for MCI‐AD patients. As expected, the tau proteins significantly positively correlated between them in every patient ΄s group and control subjects. No other significant correlations were found. Conclusion The exclusive correlation between CSF α‐syn and tau protein levels in MCI‐AD patients, support a pathophysiologic connection between the metabolisms of these proteins, even at the early stages of the illness. In our opinion, the role of α‐syn should be included into the new pathogenetic theories of AD.