Genetic and molecular biomarkers of Alzheimer's disease

Abstract

[eng] Alzheimer’s disease (AD) is the leading cause of dementia worldwide. Research in the past decade has led to major progress in understanding the genetic etiology of the disease; since I started my PhD (2019), nearly 20 genetic risk factors have been associated with late onset AD. Among them, the Ԑ4 allele of the APOE gene was the first identified, and remains the major genetic risk factor for AD. Despite extensive genetic research, a large part of the disease heritability remains elusive, the disease mechanisms incomprehensible, and targeted preventive interventions or pharmacological treatments for AD unavailable at the time. In this context, the overarching aim of the studies included in this thesis was to contribute to the knowledge of AD identifying new genetic risk factors and to better understand the role played by the APOE gene in the development of the disease. Such information would allow us to gain new insights into the molecular and biological mechanisms underlaying the disease and ultimately find new targets for treatment. This thesis provides evidence of the possible effectiveness of the use of a polygenic risk scores in a clinical setting for diagnosis of AD and actively improves the knowledge of the genetic factors associated with AD through genome-wide association studies.