Abstract

MOLECULAR MECHANISMS AND EMERGING BIOMARKERS IN ALZHEIMER’S DISEASE: IMPLICATIONS FOR PRECISION THERAPEUTICS

Miruthula U. V.*, Swetha G.T., Bharathi S.

Abstract

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuronal loss, and accumulation of amyloid-β and tau pathology. Despite rapid advances in biomarker discovery and therapeutics, AD remains a major global health challenge with no curative treatment. Objective: This review synthesizes contemporary evidence on the molecular mechanisms, genetic and epigenetic regulators, biomarker advancements, and emerging precision-medicine strategies in AD, highlighting gaps that remain barriers to effective disease modification. Content: Recent research has refined our understanding of AD as a multifactorial disorder driven by converging pathways including amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, and synaptic dysfunction. Genetic determinants—particularly APOE ε4, APP, PSEN1/2 variants—interact with epigenomic alterations such as DNA methylation drift, histone modifications, and dysregulated non-coding RNAs, collectively accelerating neurodegeneration. Advances in fluid biomarkers (CSF Aβ42, p-tau181, NfL), blood-based assays, and molecular neuroimaging (amyloid-PET, tau-PET) now enable earlier and more accurate diagnosis. Omics-driven studies have identified novel molecular signatures and therapeutic targets, including pathways regulating lipid metabolism, microglial activation, and APOE4 structure– function dynamics. Emerging interventions—such as gene editing, APOE4 structural correction, and anti-amyloid immunotherapies—show promise but require rigorous validation. Conclusion: AD pathophysiology reflects complex interactions between genetic liability, molecular dysregulation, and modifiable environmental factors. While current therapies provide symptomatic relief, advances in biomarkers and genome-guided therapeutics move the field closer to earlier detection and precision-based interventions.

Keywords: Alzheimer’s disease; biomarkers; APOE4; epigenetics; precision medicine.