Findings and advancements of next-generation sequencing in Alzheimer’s disease

Abstract

Introduction: Next-generation sequencing (NGS) has revolutionized the understanding of Alzheimer’s disease (AD), uncovering genetic and transcriptomic biomarkers that enhance the ATN (Amyloid-beta, Tau, Neurodegeneration) framework. These advancements have illuminated the roles of reactive astrocytes, amyloid deposition, and tau phosphorylation, linking neurodegeneration to specific molecular pathways.

Objective: To evaluate NGS’s impact on identifying biomarkers, understanding AD pathogenesis, and advancing personalized diagnostics and treatments.

Method: A narrative review was conducted using terms like “Alzheimer’s disease,” “nextgeneration sequencing,” “ATN framework,” and “transcriptomics.” Studies published in English, focusing on NGS in AD diagnosis or management, were included.

Result: NGS has identified genes such as APP, TREM2, and PLD3, along with epigenetic modifications linked to AD. Transcriptomic studies highlighted pathways related to inflammation, synaptic dysfunction, and neurodegeneration. Moreover, reactive astrocytes were shown to mediate beta-amyloid accumulation and tau progression.

Conclusion: While NGS has transformed AD research, challenges such as data interpretation and protocol standardization limit its clinical application. Nonetheless, its integration into the ATN model and personalized diagnostics offers promising avenues for early detection and targeted therapies.