Epigenetics in Alzheimer’s disease: from molecular mechanisms to emerging novel biomarkers

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disorder that represents the leading cause of dementia worldwide, affecting over 50 million people. This global burden is expected to rise dramatically over the coming decades because of global population aging, representing a public health concern. Despite significant advances in understanding AD pathophysiology, early diagnosis remains challenging, emphasizing the urgent need for novel, reliable diagnostic and predictive biomarkers capable of identifying individuals at risk of progression during the preclinical stages of the disease. Growing evidence indicates that epigenetics constitutes a dynamic interface through which aging and environmental exposures influence gene expression and cellular homeostasis, thereby contributing to AD susceptibility and progression. The present review summarizes current knowledge on the epigenetic landscape of AD, from canonical epigenetic mechanisms, including aberrant DNA methylation, histone modifications, and non-coding RNAs (ncRNAs), to the emerging role of mitoepigenetics and RNA methylation in disease-associated molecular mechanisms. Finally, we discuss the potential of epigenetic alterations as promising innovative biomarkers of AD, providing insights into novel avenues for diagnostic and therapeutic intervention.