AUTHOR=Mosca Alessandra , Sperduti Samantha , Pop Viorela , Ciavardelli Domenico , Granzotto Alberto , Punzi Miriam , Stuppia Liborio , Gatta Valentina , Assogna Francesca , Banaj Nerisa , Piras Fabrizio , Piras Federica , Caltagirone Carlo , Spalletta Gianfranco , Sensi Stefano L. 

TITLE=Influence of APOE and RNF219 on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer’s Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=10

YEAR=2018

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2018.00092

DOI=10.3389/fnagi.2018.00092

ISSN=1663-4365

ABSTRACT=<p>The risk for Alzheimer’s disease (AD) is associated with the presence of the 𝜀4 allele of Apolipoprotein E (<italic>APOE</italic>) gene and, recently, with a novel genetic variant of the <italic>RNF219</italic> gene. This study aimed at evaluating interactions between <italic>APOE</italic>-𝜀4 and <italic>RNF219</italic>/G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI) or AD. We enrolled a total of 173 female MCI or AD patients (83 MCI; 90 AD). Subjects were screened with a comprehensive set of neuropsychological evaluations and genotyped for the <italic>APOE</italic> and <italic>RNF219</italic> polymorphic variants. Analysis of covariance was performed to assess the main and interaction effects of <italic>APOE</italic> and <italic>RNF219</italic> genotypes on the cognitive and behavioral scores. The analysis revealed that the simultaneous presence of <italic>APOE</italic>-𝜀4 and <italic>RNF219</italic>/G variants results in significant effects on specific neuropsychiatric scores in MCI and AD patients. In MCI patients, <italic>RNF219</italic> and <italic>APOE</italic> variants worked together to impact the levels of anxiety negatively. Similarly, in AD patients, the <italic>RNF219</italic> variants were found to be associated with increased anxiety levels. Our data indicate a novel synergistic activity <italic>APOE</italic> and <italic>RNF219</italic> in the modulation of behavioral traits of female MCI and AD patients.</p>