Reelin plasma levels could identify cognitive impairment in Alcohol Use Disorder diagnosed-patients. A negative effect of peripheral APOE4 on Memory/Learning

Abstract

One of the genetic risk factors recently found to modulate cognition in alcohol consumption is the presence of the ApoE-ε4 allele. ApoE-ε4 allele codes for an aberrant APOE4 protein and there are no studies on the effect of peripheral APOE4 in Alcohol Use Disorder (AUD) patients. Reelin shares the same receptors with APOE4 (ApoER2, VLDLR) and has also been related to cognition in several pathologies. We evaluated APOE4 and Reelin plasma levels and studied their relationship with different cognitive domains in a cohort of abstinent AUD patients. 24 abstinent patients with AUD recruited from an outpatient alcohol program (Hospital Universitario 12 de Octubre, Madrid, Spain) and 34 healthy control subjects were assessed with a validated screening test for AUD, named "Test of detection of cognitive impairment in alcoholism (TEDCA)". The TEDCA identifies the presence of cognitive impairment and provides scores for general intelligence and for three cognitive domains: visuospatial cognition, memory/learning, and executive function. Plasma from patients was obtained in a time-point between 4 and 12 weeks of abstinence. Plasma APOE4 (indicative of APOE4+ carriers) and Reelin were determined by e4Quant patented technique and by Enzyme-Linked Immunosorbent Assay, respectively. We found a negative effect of plasma APOE4 presence (APOE4+) on cognition (general intelligence, memory/learning and executive function) (ANCOVA, p<0.05) and an interaction between AUD disorder and APOE4for memory/learning domain (p<0.05). Reelin was higher in patients and, interestingly, it reached higher plasma levels in patients expressing APOE4, being those with worse cognitive per formance. Reelin identified cognitive deterioration in AUD for general intelligence and executive function (binary logistic regression), explaining 42.8% and 60.0% of the variance of the presence of deficit, respectively. Reelin could be a biological diagnostic tool for early identification of cognitive impairment in AUD pathology. The co-presence of AUD and APOE4+ may favor cognitive impairment in memory/learning.