Genetic Insights and Molecular Pathways in Alzheimer's Disease: Unveiling the Complexity of Neurodegeneration

Dear Colleagues,

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive decline and complex molecular underpinnings. Genetic factors, including mutations in APP, PSEN1, and PSEN2, as well as risk variants such as APOE ε4, play pivotal roles in amyloid-β aggregation and tau pathology. Recent genome-wide association studies (GWAS) have uncovered additional susceptibility loci linked to immune response, lipid metabolism, and synaptic function, highlighting the polygenic nature of AD. At the molecular level, dysregulation of neuroinflammatory pathways, mitochondrial dysfunction, oxidative stress, and impaired proteostasis converge to accelerate neuronal loss. Advances in transcriptomics, epigenetics, and multi-omics approaches are further elucidating the interplay between genetic predisposition and environmental factors, offering insights into disease heterogeneity and therapeutic targets. Understanding these interconnected pathways is essential for the development of personalized medicine strategies aimed at early detection, prevention, and precision therapies in AD.

Dr. Marta Rusek
Dr. Alessandro Romano
Guest Editors

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