Nowadays, the amyloid cascade hypothesis is the dominant model to explain Alzheimer's disease (AD) pathogenesis. By this hypothesis, the inherited genetic form of AD is discriminated from the sporadic form of AD (SAD) that accounts for 85-90% of total patients. The cause of SAD is still unclear, but several studies have shed light on the involvement of environmental factors and multiple susceptibility genes, such as Apolipoprotein E and other genetic risk factors, which are key mediators in different metabolic pathways (e.g., glucose metabolism, lipid metabolism, energetic metabolism, and inflammation). Furthermore, growing clinical evidence in AD patients highlighted the presence of affected systemic organs and blood similarly to the brain. Collectively, these findings revise the canonical understating of AD pathogenesis and suggest that AD has metabolic disorder features. This review will focus on AD as a metabolic disorder and highlight the contribution of this novel understanding on the identification of new biomarkers for improving an early AD diagnosis.
Keywords: Type-3-Diabetes; adipose tissue dysfunction; amyloid cascade hypothesis; energetic metabolism; glucose metabolism; lysosomes dysfunction; neurodegeneration; neuroinflammation.