AUTHOR=Strafella Claudia , Caputo Valerio , Termine Andrea , Fabrizio Carlo , Calvino Giulia , Megalizzi Domenica , Ruffo Paola , Toppi Elisa , Banaj Nerisa , Bassi Andrea , Bossù Paola , Caltagirone Carlo , Spalletta Gianfranco , Giardina Emiliano , Cascella Raffaella 

TITLE=Identification of Genetic Networks Reveals Complex Associations and Risk Trajectory Linking Mild Cognitive Impairment to Alzheimer’s Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 14 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.821789

DOI=10.3389/fnagi.2022.821789

ISSN=1663-4365

ABSTRACT=Amnestic mild cognitive impairment (aMCI) and sporadic Alzheimer’s disease (AD) are multifactorial conditions resulting from a complex crosstalk among multiple molecular and biological processes. The present study investigated the association of variants localized in genes and miRNAs with aMCI and AD, which may represent susceptibility, prognostic biomarkers or multi-target treatment options for such conditions. The study included 371 patients (217 aMCI and 154 AD) and 503 healthy controls, which were genotyped for a panel of 120 single nucleotide polymorphisms (SNPs) and, subsequently, analyzed by statistical, bioinformatics and machine-learning approaches. As a result, 21 SNPs and 13 SNPs were associated with aMCI and sporadic AD, respectively. Interestingly, a set of variants shared between aMCI and AD displayed slightly higher Odd Ratios in AD with respect to aMCI, highlighting a specific risk trajectory linking aMCI to AD. Some of the associated genes and miRNAs were shown to interact within the signaling pathways of APP (Amyloid Precursor Protein), ACE2 (Angiotensin Converting Enzyme 2), miR-155 and PPARG (Peroxisome Proliferator Activated Receptor Gamma), which are known to contribute to neuroinflammation and neurodegeneration. Overall, this study revealed interesting insights concerning the genetic factors contributing to the neuroinflammatory and neurodegenerative mechanisms underlying aMCI and sporadic AD, which could be exploited to develop personalized approaches based on the individual genetic make-up and multi-target treatments.